THESIS FILESObesity is a medical condition in

Transcription

A POLYHERBAL FORMULATION FOR HYPERLIPIDEMIA
(ANCIENT MEDICINE MODERN TARGETS)
Dr. Imtiaz Ahmed Channa
MBBS, MS (Ortho), POA,
Fellowship in Hip & Knee Replacement Surgery
Dr. Kiran Saroor
M.PHIL. / PHD, B-PHARM, MBA, Oncology certified, Resident in
Oncology, Research Fellow at Karachi University
Published by:
Jabbar’s Printers
Shop No. 11, Adeel Luxury Appartment, Opp. Baber Square
Karimabad Karachi Pakistan
OCTOBER 2015
Email: [email protected]
DEDICATION
THIS BOOK IS DEDICATED TO MY MOTHERS HASEENA KHATOON (LATE) & IFFAT JAHAN
(LATE).
WITHOUT THEIR GUIDANCE & LOVE I AM NOTHING.
LOVE YOU MOM’S
DR. KIRAN SAROOR
TABLE OF CONTENTS
Title
Page No.
CHAPTER 1
1.INTRODUCTION
1-3
1.1.CLASSES OF ANTI-OBESITY DRUGS
3
1.1.1.ESTABLISHED CLASSES
3
1.1.1.1.STATIN
3-4
1.1.1.2.FIBRATES
4
1.1.1.3.NIACIN
4
1.1.1.4.BILE ACID SEQUESTRANTS
4-5
1.1.1.5.EZETIMIBE
5
1.1.1.6.PHYTOSTEROL
5
1.1.1.7.ORLISTAT
5
1.1.2.INVESTIGATIONAL CLASSES
6
1.2.HERBS FOR WT LOSS AND SIDE EFFECTS 6
1.2.1.ASTRAGALUS
6
1.2.2.BEE POLLEN
7
1.2.3.BLADDER WREK
7
1.2.4.BREWERS YEAST
7
1.2.5.COCONUT OIL
7-8
1.2.6.MEDIUM CHAIN AND LONG CHAIN TRIGLYCERIDES 8-9
1.2.7.DANDELION
9-10
1.2.8.EVENING PRIMROSE
10
1.2.9.FENNEL
10
1.2.10.FENU GREEK
10
1.2.11.GREEN TEA
10
1.2.12.KELP
10-11
1.2.13.LICORICE
11
1.2.14.MALABAR TAMARIND
12
1.2.15.PINRAPPLE
12
1.2.15(a).PLANTAIN OR PSYLLIUM
13
1.2.16.RED PEPPER AND OTHER SPICES
13
1.2.17.SIBERIAN GINSENG
13-14
1.2.18.WALNUT
14
1.2.19.BOJENMI CHINESE TEA
14
1.2.20.OTHERS
15-16
1.3.MECHANISM OF ACTION OF ANTI -
17
OBESITY DRUGS
1.3.1.DRUGS FOR OBESITY CONTROL
17
1.3.1.1.NIACIN
18
1.3.1.1.1.NIACIN EFFECT ON LIPID METABOLISM
19
1.3.1.2.FIBRATES
19
1.3.1.2.1.FIBRATES EFFECT ON HDL
20
1..3.1.3.STATINS(HMG COA REDUCTASE INHIBITORS)
20
1.3.1.3.1.EFFECTS OF SIMVASTATIN ON TGRL
21
METABOLISM
1.3.1.4.OMEGA 3 FATTY ACIDS
21
1.3.1.4.1.CONVERSION OF LINOLEIC ACID TO LONG CHAIN 22
DERIVATES
1.4.MORTALITY
22-23
1.5.MORBIDITY
23
1.6.EFFECTS OF OBESITY ON DIFFERENT
24-25
BODY SYSTEMS
1.7.FACTORS OF OBESITY
26
1.7.1.FACTOR 1 (DIET)
26-27
1.7.2.FACTOR 2 (SEDENATRY LIFE STYLE)
27-28
1.7.3.FACTOR 3 (GENETICS)
28-29
1.7.4.FACTOR 4 (OTHER ILLNESS)
29
1.7.5.FACTOR 5 (SOCIAL DETERMINATION)
29-30
1.7.6.PATHOPHYSIOLOGY
30-31
1.8.PLANT DESCRIPTION
31
1.8.1.PLANT A (Cinnamomum cassia blume)
31
1.8.1.1.SCIENTIFIC CLASSIFICATION
31-32
1.8.1.2.TAXONOMICAL ENUMERATION
32
1.8.1.3.MEDICINAL USES
32-33
1.8.1.4.CHEMICAL AND BIOLOGICAL SURVEY
33
1.8.2.PLANT B(Commiphora wightii)
33
33-34
34
35
35
1.8.3.PLANT C (Embelica officinalis)
35
35-36
36-37
37
37-38
1.8.4.PLANT D (Ferula foetida L)
38
1.8.4.1.SCIENTIFIC
38-39
CLASSIFICATION,HABITAT,CULTIVATION
1.8.4.2.MEDICNAL USES
39
40
CHAPTER 2
40
2.INTRODUCTION
40-41
2.1.PARAMETERS FOR CRUDE DRUG
41-42
EVALUATION
2.1.1.QUALITATIVE CHEMICAL EVALUATION
42
2.2.IDENTIFICATION POF PLANTS
43
2.2.1.PLANT A(Cinnamomum cassia)
43
2.2.1.1.ORGANOLEPTIC EVALUATION OF PLANT A
44-45
2.2.1.2.ORGANOLEPTIC EVALUATION OF PLANT A BY
46
CHART
2.2.1.3.POWDER MICROSCOPY OF PLANT A
47
2.2.1.4.HISTOLOGY OF PLANT A
47-48
2.2.2.PLANT B (Commiphora wightii)
49
2.2.2.1.ORGANOLEPTIC EVALUATION OF PLANT B
50-51
2.2.2.2.ORGANOLEPTIC EVALUATION OF PLANT B BY
52
CHART
2.2.2.3.POWDER MICRSCOPY OF PLANT B
53
2.2.2.4.HISTOLOGY OF PLANT B
54-55
2.2.3.PLANT C (Embelica officinalis)
56
2.2.3.1.ORGANOLEPTIC EVALUATION OF PLANT C
57-58
2.2.3.2.ORGANOLEPTIC EVALUATION OF PLANT C BY
59
CHART
2.2.3.3.POWDER MICROSCOPY OF PLANT C
60
2.2.3.4.HISTOLOGY OF PLANT C
61-63
2.2.4.PLANT D(Ferula foetida L)
64
2.2.4.1.ORGANOLEPTIC EVALUATION OF PLANT D
65-66
2.2.4.2.ORGANOLEPTIC EVALUATION OF PLANT D BY
67
CHART
2.2.4.3.IDENTIFICATION TESTS OF PLANT D
68
2.2.5.REDUCIN
69
2.2.5.1.POWDER MICROSCOPY OF REDUCIN
69-70
CHAPTER 3
71
3.EXPERIMENTAL STUDIES
71
3.1.APPARATUS
71-73
3.2.MATERIAL AND METHOD
73
3.3.SOLVENTS
74
3.3.1.SOLVENT SYSTEM USED IN CHROMATOGRAPHY
75
3.4.BEHAVIOUR OF POWDER
76
3.4.1.BEHAVIOR OF POWDER WITH DIFFRENT CHEMICAL 76
REAGENTS (PLANT B
3.4.2.BEHAVIOR OF POWDER WITH DIFFRENT CHEMICAL 77
REAGENTS (PLANT C)
3.4.3.BEHAVIOUR OF POWDER WITH DIFFRENT
78
CHEMICAL REAGENTS (PLANT D)
3.5.PHYTOCHEMICAL ANALYSIS OF PRIMARY 79
AND SECONDRY METABOLITES (PLANTS A-D)
3.5.1.PHYTOCHEMICAL ANALYSIS OF PLANT A
79
3.5.2.PHYTOCHEMICAL ANALYSIS OF PLANT B
80
3.5.3.PHYTOCHEMICAL ANALYSIS OF PLANT C
81-82
3.5.4.PHYTOCHEMICAL ANALYSIS OF PLANT D
82
3.6.EXTRACTION AND ISOLATION
83
PROCEDURES
3.6.1.EXTRACTION AND ISOLATION OF REDUCIN POWDER 83
3.6.2.EXTRACTION OF PLANT DRUG A-D FOR
84
PHYTOCHEMICAL AND CHROMOGENIC TESTING
3.6.3.CHROMATOGRAM DEVELOPMENT FOR TLC
85-89
CHROMATOGRAPHY
CHAPTER 4
90
4.CLINICAL STUDIES OF REDUCIN
90
4.1.INTRODUCTION
90
4.1.1.CONSEQUENCES OF OBESITY
91
4.1.2.SCREENING AND DIAGNOSIS
92
4.1.3.WAIST CIRCUMFERENCE
92
4.1.4.MEDICATION PROMOTE WT GAIN
93
4.1.5.CLASSIFICATION OF OBESITY AND DISEASES
94
4.1.6.METABOLIC SYNDROME
94-95
4.1.6.1.DIAGNOSTIC CRITERIA
95-96
4.2.MANAGMENT OF OBESITY
96
4.2.1.THE 5As FOR TREATMENT OF OBESITY
96
4.2.2.PHARMACOTHERAPY
97
4.2.3.BARIATRIC SURGERY
98
4.3.CLINICAL STUDIES OF REDUCIN
98
4.3.1.PROVEN THERAPEUTIC EFFICENCY OF HERBAL
DRUGS (A-D)IN LITERATURE
98
4.3.1.1.PLANT A (Cinnamomum cassia)
98
4.3.1.2.PLANT B (Commiphora wightii)
98-99
4.3.1.3.PLANT C (Embelica officinalis)
99
4.3.1.4.PLANT D (Ferula foetida)
99-100
4.3.2.ANIMAL TRIALS
100
4.3.2.1.AIMS AND OBJECTIVES
100
4.3.2.2.CONDUCTION AND EVALUATION OF STUDIES
100-101
4.3.2.3.TRIAL I
101
4.3.2.4.TRIAL II
101-102
4.3.2.5.RESULTS
103
4.3.2.5.1.EFFECTS OF REDUCIN ON SERUM LIPID PROFILE 104
OF ADULT MALE RATS (A V/S B)
4.3.2.5.2.EFFECTS OF FATTY MIXTURE FEEDING DIET ON
SERUM MALE RATS(A V/S C)
105
4.3.2.5.3.EFFECTS OF REDUCIN ON LIPID PROFILE (C V/S
D)
106
4.3.2.6.DISCUSSION
107-108
4.4.EXPERIMENTAL CONDITIONS OF
CLINAICAL TRIALS OF REDUCIN
108
4.4.1.CONDUCTION AND EVALUATION OF CLINICAL
TRIALS
108
4.4.1.1.PARTICIPANTS
108
4.4.1.2.DOSAGE PROTOCOL
109
4.4.1.3.MEASUREMENT OF NEW OUT COMES
109
4.4.1.4.METHOD
109-110
4.4.1.5.DIAGNOSTIC CRITERIA
110
4.4.1.5.1.TYPES OF OBESITY
110-111
4.4.1.5.2.SIGN AND SYMPTOMS OF OBESITY
112-114
4.4.1.5.3.GENERAL PATIENT CRITERIA
115
4.4.1.6.COMPARITIVE STUDIES OF GENERAL PATIENT
CRITERIA
115=116
4.4.1.7(a).GROUP A NORMAL DIET GENERAL HEALTH
EXISTING DISEASE
117
4.4.1.7(b).GROUP B RICH FAT DIET HEALTH EXISTING
DISEASE
118
4.5.DIAGNOSIS
119
4.5.1.BASIS OF DIAGNOSIS
119
4.5.2.ASSESMENT OF CHOLESTEROL LEVEL BEFORE AND
AFTER TREATMENT OF REDUCIN
120
4.5.2.1.ASSESMENT OF CHOLESTEROL LEVEL BEFORE AND 120
AFTER TREATMENT OF REDUCIN IN NORMAL DIET GP.
4.5.2.2.ASSESMENT OF CHOLESTEROL LEVEL BEFORE AND 121
AFTER TREATMENT OF REDUCIN IN RICH FAT DIET GP
4.5.3.REDUCE HDL LEVELS BEFORE AND AFTER
TREATMENT
122
4.5.3.1.REDUCED HDL LEVELS BEFORE AND AFTER
TREATMENT OF REDUCIN IN MEN
122
4.5.3.2.REDUCED HDL LEVELS BEFORE AND AFTER
TREATMENT OF REDUCIN IN WOMEN
123
4.5.4.REDUCED WAIST CIRCUMFERENCE BEFORE AND
AFTER TREATMENT OF REDUCIN
124
4.5.4.1.REDUCED WAIST CIRCUMFERENCE AFTER
TREATMENT OF REDUCIN IN MEN
124
4.5.4.2.REDUCED WAIST CIRCUMFERENCE AFTER
TREATMENT OF REDUCIN IN WOMEN
125
CHAPTER 5
126
5.PHYTOCHEMICAL STUDIES
126
5.1.FORMULATION OF ORAL DOSAGE FPRM OF REDUCIN 126
5.2.MATERIAL AND METHOD
126
5.2.1.AUTHENTICATION OF DRUG
126
5.2.2.CLEANSING AND DRYING
127
5.2.3.GRINDING
127
5.2.4.PERCOLATION AND LYOPHILIZATION
127
5.2.5.FLOW ABILITY OF POWDER
128
5.2.6.ANGLE OF REPOSE OF POWDER
128-129
5.2.7.POROSITY OF POWDER
129-132
5.3.PHYSIOCHEMICAL FEATURES OF REDUCIN
132
5.3.1.WT VARIATION
132-136
5.3.2.DISINTEGRATION
137-138
5.3.3.DISSOLUTION
139-140
CHAPTER 6
141
6.RESULTS AND DISCUSSION
141-142
6.1.PHARMACOGNOSTIC EVALUATION OF
PLANT DRUG (A-D)
142
6.1.1.CHARACTERISTIC FEATURES OF PLANT A
143
6.1.2.CHARACTERISTIC FEATURES OF PLANT B
144-145
6.1.3.CHARACTERISTIC FEATURES OF PLANT C
145-146
6.1.4.CHARACTERISTIC FEATURES OF PLANT D
146-147
6.1.5.CHARACTERISTIC FEATURES OF REDUCIN
147
6.2.PHYTOCHEMICAL EVALUATION OF PLANT DRUGS (A- 148-149
D)
6.3.CLINICAL STUDIES ON REDUCIN
150-151
6.4.PHYTOPHARMACEUTICAL STUDIES OF REDUCIN
152
REFRENCES
153210
CHAPTER 1.INTRODUCTION:
Obesity is a medical condition in which excess body fat has accumulated to
the extent that it may have a negative effect on health leading to reduce life
expectancy and or increase health problems.
Obesity increases the occurrence of various diseases especially heart
diseases, type 2 diabetes, obstructive sleep apnea, certain type of cancer and
osteoarthritis .
Obesity is most commonly caused by combination of excessive food, energy
intake, lack of physical activity and genetic susceptibility. A few cases are caused
by genes, endocrine disorders, medications and psychiatric illness, evidence to
support the view that some obese people eat little yet, gain weight due to a slow
metabolism is limited.
Dieting and exercising are the main treatment for obesity. Diet quality can
be improved by reducing the consumption of energy dense foods such as those
high in fat and sugars and by increasing the intake of dietary fiber with a suitable
diet. Anti-obesity drugs may be taken to reduce appetite or decrease fat
absorption. If diet, exercise and medications are not effective, a gastric balloon
may assist with weight loss or surgery may be performed to reduce stomach
volume or bowel length, leading to feeling full earlier and a reduce ability to
absorb nutrient foods.
Basically obesity is a medical condition in which excess body fat has
accumulated to the extent that it may have an adverse effect on health. It is
define by body mass index.
BMI is defined as the subject weight divided by the square of their height
and is calculated as follows:- BMI = m
h2
Where m and h are the subjects wt and height respectively.
BMI is usually expressed in Kg per square meter, resulting when wt is
measured in kilograms and height in meters. To convert from pounds per square
inch multiply by 703 (kg/m2) (1b/sq in) .
The most commonly used definition established by the WHO in 1997 and
published in 2000, provides the value listed in the table.
BMI
From
(kg/m2)
Upto
18.5
Classification
18.5
25.0
Normal wt
25.0
30.0
Over wt
30.0
35.0
Class I obesity
35.0
40.0
Class II obesity
40.0
Under wt
Class III obesity
Obesity has harmful effect on health leading to various types of diseases
like cardiovascular diseases, diabetes mellitus type 2, and obstructive sleep apnea,
certain type of cancers, osteoarthritis and asthma.
1.1. Classes of Anti-Obesity Drugs:
There are several classes of hypolipidemic drugs. They may differ in both their
impact on the cholesterol profile and adverse effects. For example, some may
lower the "bad cholesterol" low density lipoprotein (LDL) more so than others,
while others may preferentially increase high density lipoprotein (HDL), "the good
cholesterol". Clinically, the choice of an agent will depend on the patient's
cholesterol profile, cardiovascular risk, and the liver and kidney functions of the
patient, evaluated against the balancing of risks and benefits of the medications.
1.1.1. Established Classes:
1.1.1.1. Statins:
Statins are particularly well suited for lowering LDL, the cholesterol with the
strongest links to vascular diseases. In studies using standard doses, statins have
been found to lower LDL-C by 18% to 55%, depending on the specific statin being
used. There is a risk of severe muscle damage (myopathy & rhabdomyolysis) with
statins. Hypercholesterolemia is not a risk factor for mortality in persons older
than 70 years and risks from statin drugs are more increased after age 85.
1.1.1.2. Fibrates:
Fibrates are indicated for hypertriglyceridemia. Fibrates typically lower
triglycerides by 20% to 50%. Level of the good cholesterol HDL is also increased.
Fibrates may decrease LDL, though generally to a lesser degree than statins.
Similar to statins, there is a risk of severe muscle damage (myopathy &
rhabdomyolysis).
1.1.1.3. Niacin:
Niacin like fibrates, is also well suited for lowering triglycerides by 20–50%. It may
also lower LDL by 5–25% and increase HDL by 15–35%. Niacin may cause
hyperglycemia and may also cause liver damage. The niacin derivative acipimox is
also associated with a modest decrease in LDL.
1.1.1.4. Bile Acid Sequestrants:
They are particularly effective for lowering LDL-C by sequestering the cholesterolcontaining bile acids released into the intestine and preventing their reabsorption
from the intestine. It decreases LDL by 15–30% and raises HDL by 3–5%, with little
effect on triglycerides but can cause a slight increase. Bile acid sequestrants may
cause gastrointestinal problems and may also reduce the absorption of other
drugs and vitamins from the gut.
1.1.1.5. Ezetimibe (Zetia):
It is a selective inhibitor of dietary cholesterol absorption.
Lomitapide (Juxtapid) is a microsomal triglyceride transfer protein (MTP) inhibitor.
1.1.1.6. Phytosterols:
It may be found naturally in plants. Similar to ezetimibe, phytosterols reduce the
absorption of cholesterol in the gut. Hence, they are most effective when
consumed with meals. However, the precise mechanism of action of phytosterols
differs from ezetimibe.
1.1.1.7. Orlistat (Xenical): Its primary function is to prevent the
absorption of about 30% of fats from the human diet, thereby reducing caloric
intake. A drug designed to treat obesity, it works by inhibiting pancreatic lipase, an
enzyme that breaks down triglycerides in the intestine.
1.1.2. Investigational Classes:
CETP inhibitors (cholesteryl ester transfer protein). It is expected that these drugs
will mainly increase HDL while lowering LDL;
Squalene synthase inhibitor.
ApoA-1 Milano.
Hccinobucol(AGI-1067), a novel antioxidant, failed a phase 3 trial
Apoprotein-B inhibitor Mipomersen (approved by the FDA in 2013 homozygous
familial hypercholesterolemia).
PCSK9 Monoclonal antibody inhibitors.
1.2. Herbs for Weight Loss & Side Effects:
There are many herbal plants used as antilipidemic agents,some of them are as
follow
1.2.1. Astragalus (Astragalus gummifer):
Astragalus increases energy and improves nutrient absorption.
SIDE EFFECTS: Do not use this herb in the presence of a fever.
1.2.2. Bee pollen:
Bee pollen stimulates the metabolism and helps to curb appetite. Take up to 1
teaspoon daily.But reports of over stimulation are here.
1.2.3. Bladderwrack (Fucus vesiculosus):
Bladderwrack contain iodine, which helps to enhance thyroid function. Dosage:
Take 150 milligrams at breakfast and another 150 milligrams at lunch for two
months.
SIDE EFFECTS: Check with your doctor before taking this herb if you have a thyroid
disorder, high blood pressure, or heart problems. If you are allergic to shellfish
and/ or sensitive to iodine, do not take this herb. Also do not take kelp and
bladderwrack at the same time.
1.2.4. Brewer’s yeast&Chick Weed:
Brewer's yeast will help to reduce various cravings for food and drink.
Chickweed (Stellaria media):
This herb a great folk reputation for shedding weight.
1.2.5. Coconut oil:
Coconut oil, extracted from coconuts, is a rich source for medium chain
triglycerides. Medium chain triglycerides (MCTS) are special types of saturated
fats separated out from coconut oil that range in length from six to twelve carbon
chains. Unlike regular fats, MCTs do not appear to cause weight gain; they actually
promote weight loss.
1.2.6. Medium Chain Triglycerides and Long Chain
Triglycerides:
Medium chain triglycerides (MCTS) are special types of saturated fats separated
out from coconut oil. It range in length from six to twelve carbon chains.
The long-chain triglycerides (LCTS) are the most abundant fats found in nature.
LCTs are the storage fat for both humans and plants. They range in length from
eighteen to twenty-four carbons.
MCTs are used by the body differently than LCTs. This is because of the difference
in length of carbon chains. The larger LCTs are difficult for the body to metabolize.
So the body tends to store these fats. MCTS, on the other hand, are easy to
metabolize. So, they are rapidly burned as energy. They also promote the burning
of LCTs.
Because of the way body handles MCTs, MCTs do not appear to cause weight gain
like the conventional fats do. They, in fact, actually promote weight loss. LCTs are
usually stored in the fat deposits. Since their energy is conserved, a high fat diet
decreases the metabolic rate. Lower the metabolism, higher the weight gain.
Scientists suggest that medium-Chain Triglycerides promote weight loss by
increasing thermogenesis (heat production). Thermogenesis is the method by
which the body "wastes" calories. There is evidence that the level of diet-induced
thermogenesis is what determines whether an individual is likely to be
overweight. In lean individuals, a meal may stimulate up to a forty-percent
increase in heat production. In contrast, overweight individuals often experience
only a ten-percent or less increase in heat production. The food energy is stored
instead of being converted to heat. In actuality, the food is more efficiently
converted in case of LCTs. So, there is less need for them to obtain the same
energy. (LCTs is like a fuel efficient car. It needs less fuel to go to the same distance
as compared to a fuel guzzling car (like MCTs). So, for the same food consumption,
LCTs will have more fat stored in the body promoting weight gain.
Researchers concluded that substituting MCTs for LCTs in your diet would produce
weight loss as long as the calorie level remained the same.
Recommended Dosage: 1 to 2 tablespoons per day.
1.2.7.Dandelion (Taraxacum officinale):
Dandelion may flush out the kidneys, boost metabolism, and off- set a craving for
sweets. Eat the leaves raw in a salad or make a tea by boiling 2 to 3 tsp of the root
in a cup of water for I 0 to 15 minutes. Drink three times a day.
1.2.8. Evening primrose (Oenothera biennis):
This herb is a good source for tryptophan which is believed to help in weight loss.
Take a half-teaspoon of evening primrose oil three times a day.
1.2.9. Fennel (Foeniculum vulgare):
Fennel removes mucus and fat from the intestinal tract, and is a natural appetite
suppressant.
1.2.10. Fenugreek (Trigonella foenum-graecum):
Fenugreek is useful for dissolving fat within the liver.
1.2.11. Green Tea (Camellia sinensis):
Green tea enhances the ability of the body to burn fat. Choose a standardized
extract containing 50 percent catechin and 90 percent total polyphenols and take
300 milligrams thirty minutes before breakfast and another thirty minutes before
lunch. Do not take more.
1.2.12. Kelp (Fucus spp.):
Kelp is a type of seaweed that’s rich in antioxidant vitamins and iodine. It is
believed to stimulate a hormone produced by the thyroid gland that’s responsible
for boosting metabolism, so you’ll burn more calories by the hour. You can also get
other kinds of seaweed in your diet by adding them to soups and salads. Kelp is
very useful for thyroid-related obesity.
Dosage: Take 300-1,500 mg daily as directed on the label.
SIDE EFFECTS: Check with your doctor before taking kelp if you have a thyroid
disorder, high blood pressure, or heart problems.
1.2.13.Licorice (Glycyrrhiza glabra):
Licorice root strengthens the adrenal glands, thus helping to sustain a regulated
blood-sugar level and reduce cravings for sweets. Licorice tastes sweet.
Dose: Take a cup of licorice daily, one week out of every month for up to three
months. Licorice can also be added to other teas to sweeten them.
SIDE EFFECTS: Do not take licorice by itself on a daily basis for more than five days
at a time, as it can elevate blood pressure. Do not take it at all if you have high
blood pressure. This herb should be used with caution. Check the herbal database
for other important safety information.
1.2.14.Malabar tamarind:
The Malabar tamarind is a yellowish fruit that is about the size of an orange, with
a thin skin and deep furrows similar to an acorn squash. It is native to southern
India, where it is dried and used extensively in curries (especially fish). It looks
black when dried.
The dried fruit of Malabar Tamarind contains about thirty percent hydroxycitric
acid. It is a powerful lipogenic inhibitor. (Lipogenic inhibitor is a substance which
helps prevent the production of fat).
In addition to inhibiting the production of fat, hydroxycitrate may also suppress
appetite.
Note that hydroxycitrate only inhibits the conversion of carbohydrates into fat. It
will have no effect if a high-fat diet is consumed.
Recommended Dosage: 500 mg three times per day. Take it along with a
supplement of Chromium for best results.
1.2.15. Pineapple (Ananas comosus):
Pineapple contains an enzyme called bromelain, which helps digest both proteins
and fats.
1.2.15(a).Plantain or psyllium (Plantago):
Psyllium is the seed of Plantain. Metamucil is a commercial product that contain
psyllium.
Herbalists say that the weight-loss effect of plantain and psyllium is related to the
spongy fiber (mucilage) in the seeds and to specific chemicals (polyphenols) in the
leaves.
Dose: Take a teaspoonful of psyllium mixed well with a glass of juice or water. Take
it before each meal.
SIDE EFFECTS: If you are allergic to this herb, stop its use immediately.
1.2.16. Red pepper (Capsicum), Hit Mustard, and other
hot spices:
Scientists have found that people who took hot spicy foods (adding a teaspoon of
red-pepper sauce and a teaspoon of mustard to meal) raised their metabolic rates
by as much as 25 percent. The hot spice also stimulates thirst, so you drink more
liquids that also helps in gaining less weight.
1.2.17. Siberian Ginseng (Eleutherococcus Senticosus):
Siberian ginseng helps to stabilize blood sugar and reduce cravings for sweets. It is
also a natural energizer.
Dose: Choose a standardized extract containing 0.5 percent eleutheroside E and
take 100 milligrams daily, two weeks out of every month, for up to three months.
SIDE EFFECTS: Do not use if you have high blood pressure.
1.2.18. Walnut (Juglans):
A study of more than 25,000 Seventh-Day, Adventists showed that those who ate
the most nuts were the least obese. Walnuts are rich in serotonin. Serotonin is
shown to make us feel full; so we eat less as a result.
1.2.19. Bojenmi Chinese Tea (Reduce Fat Tea):
This Chinese herbal formula is useful for combating weight gain and obesity. It has
beneficial effects on the Stomach and Spleen, dispels Dampness and phlegm,
invigorates Qi, promotes urination, and reduces fat.
Dosage: Steep one bag per cup of water; drink up to three cups a day.
Alisma, astragalus, and atractylodes is a Chinese herbal combination that helps to
encourage weight loss. Alisma is a diuretic; astragalus enhances energy;
atractylodes helps the digestion of carbohydrates. These three herbs work best
when taken together. Select a combination formula and take one dose, as directed
on the product label, two to three times daily.
1.2.20. Other Herbs:
Combine 1 tbsp. of yarrow and 1 tbsp. of sea weed. Pour 1 cup of boiling water
over 1 tsp. of this mix, steep for eight minutes, strain and drink 1 cup three times
daily for one to two weeks.
Other slimming herbs often included in herbal tea mixtures include kelp,
chickweed, dandelion, sage, hawthorn berries, licorice root, papaya leaves, anise,
wormwood, black alder bark, lovage and saffron.
Alfalfa, com silk, dandelion, gravel root, horsetail, hydrangea, hyssop, juniper
berries, oat straw, parsley, seawrack, thyme, uva ursi, white ash, and yarrow can
be used in tea form for their diuretic properties.
Butcher's broom, cardamom, cayenne, cinnamon, Garcinia cambogia, ginger,
green tea, and mustard seed are thermogenic herbs that improve digestion and
aid in the metabolism of fat.
SIDE EFFECTS: Do not use cinnamon in large quantities during pregnancy.
Bladderwrack, borage seed, hawthorn berry, licorice root, and sarsaparilla
stimulate the adrenal glands and improve thyroid function.
SIDE EFFECTS: If overused, licorice can elevate blood pressure. Do not use this
herb on a daily basis for more than seven days in a row. Avoid it completely if you
have high blood pressure.
Ephedra,guarana and kola nut are appetite suppressants.
SIDE EFFECTS:Do not use ephedra if you suffer from anxiety,glaucoma,
Heart disease,high blood pressure ,insomnia or if you take MAO inhibitor
Drug for depression.
Note: to the high incidence of abuse of the ephedra and the resultant deaths
and serious injuries, FDA has banned the sale of ephedra in the US. A number
of other countries have banned the use of ephedra too. We recommend that
you do not use or buy any products with ephedra.
Siberian ginseng aids in moving fluids and nutrients throughout the body, and
reduces the stress of adjusting to new eating habits.
SIDE EFFECTS: Do not use this herb if you have hypoglycemia, high blood
pressure, or a heart disorder.
As we discuss above all herbal drugs have mild to severe side effects. Now we
take a look towards mechanism of action of antilipidemic agents.
1.3. Mechanism of Action of Anti obesity Drugs:
These are 4 classes of FDA-approved drugs, all of which have an indication for
reducing triglyceride.
1.4. Mortality:
Obesity is one of the leading causes of death worldwide. Large scale
American and European studies have found that mortality risk is lowest at BMI of
20-25 kg/m2 in now smokers and at 24-27 kg/m2 in Asia risk begin to increase
b/w 22-25 kg/m2 .
A BMI above 32 kg/m2 has been associated with a double mortality rate
among women over a 16 years period. In the USA, obesity in estimate to cause
111,909 to 365,000 deaths per year, while 1 million (7.7%) of death in Europe are
attributed to excess (wt [3/32]) on average obesity reduce life expectancy by 6 to
7 years, a BMI of 30-35 (kg/m2) reduce life expectancy by 2 to 4 years while severe
obesity (BMI > 40 kg/m2) reduces life expectancy by 10 years.
1.5. Morbidity:
Obesity increases the risk of many physical and mental conditions. These co
morbidities are combination of medical disorder which includes diabetes mellitus
type 2, H.B.P, H.B.C and high triglycerides levels.
Health consequences fall in to two broad categories, those attributable to
the effects of increased fat mass (such as osteoarthritis, obstructive sleep apnea,
and social stigmatization) and those due to increased no. of fat cells (diabetes,
cancer, cardiovascular disease, non- alcoholic fatty liver diseases. Increase in body
fat alter the body response to insulin, potentially leading to insulin resistance.
Increased fat also creates a pro inflammatory state and a prothrombic state. The
table given below shows the effect of obesity on different body systems.
1.6.EFFECT of Obesity on diffrent Body Systems:
Medial field
Cardiology
•
Condition
Coronary
Medical field
Dermatology
heart disease
angina
Endocrinolog
y
•
and
reproductive
•
medicine
•
Condition
Stretch marks
•
Acanthosis
and
nigricans
myocardial
•
Lymphedema
infarction
•
Cellulitis
•
Hirsutism
•
Intertigo
•
Gastroesophageal
Diabetes
Gastrointestin
mellitus
al
reflux disease
Polycystic
•
Fatty liver disease
ovarian
•
Cholelithiasis
syndrome
•
(gallstones)
Menstrual
disorders
•
Infertility
•
Complications
during
pregnancy
•
Birth defects
•
Intrauterine
fetal death
Neurology
•
Stroke
•
Meralgia
Oncology
•
Esophageal
•
Cobrectal
paresthetica
•
Pancreatic
•
Migarines
•
Gall bladder
•
Carpal
•
Endometrial
syndrome
•
Kidney
•
Dementia
•
Leukemia
•
Idiopathic
•
Malignant
tunnel
intracranial
melanoma
hypertension
•
Multiple
sclerosis
Psychiatry
•
Depression
in Respirology
•
women
•
Obstructive
sleep
apnea
Social
•
stigmatization
Obesity
hypoventilation
syndrome
•
Asthma
•
Increased
complications
during
general
anaesthesia
Rheumatolog
•
Gout
y
•
Poor mobility
Urology and
•
Erectile
dysfunction
•
Urinary
incontinence
1.7. Factors:
There are many factors which involve to produce obesity.
1. Factor 1 (Diet)
2. Factor 2 (Sedentary Life Style)
3. Factor 3 (Genetics)
4. Factor 4 (Other illness)
5. Factor 5 (Social Determinants)
1.7.1. Factor 1 (Diet)
Dietary energy supply per capita varies markedly between different regions and
countries. It has also changed significantly overtime. From the early 1970s to the
late 1990s the average food energy available per person per day (the amount of
food bought) increased in all parts of the world except Eastern Europe. The United
States had the highest availability with 3, 654 calories (15,290 kJ) per person in
1996. This increased further in 2003 to 3,75 calories (15,710) kJ). During the late
1990s Europeans had 3,394 calories (14,200 kJ) per person, in the developing
areas of Asia there were 2,648 calories (11,080 kJ) per person, and in sub-Saharan
Africa people had 2,176 calories (9,100) kJ) per person. Total food energy
consumption has been found to be related to obesity.
The widespread availability of nutritional guidelines has done little to
address the problem of overeating and poor dietary choice. From 1971 to 2000,
obesity rates in the United States increased from 14.5% to 30.9%. During the same
period, an increase occurred in the average amount of food energy consumed. For
women the average increase was 335 calories (1,400 kJ) per day (1,542 calories
(6,450 kJ) in 1971 and 1,877 calories (7,850 kJ) in 2004, while for men the average
increase was 168 calories (700 kJ) per day (2,450 calories (10,300 kJ) in 1971 and
2,618 calories (10,950 kJ) in 2004). Most of this extra food energy came from an
increase in carbohydrate consumption rather than fat consumption. The primary
sources of these extra carbohydrates are sweetened beverages, which now
account for almost 25 percent of daily food energy in young adults in America,
and potato chips. Consumption of sweetened drinks such as soft drinks, fruit
drinks, iced tea, and energy and vitamin water drinks is believed to be
contributing to the rising rates of obesity and to an increased risk of metabolic
syndrome and type 2 diabetes.
1.7.2.Factor 2: Sedentary Life Style:
A sedentary life style plays a significant role in obesity. Worldwide there has been
a large shift towards less physical demanding work and currently atleast 30% of
the world population gets in sufficient exercise gets in sufficient exercise. This is
primarily due to increasing use of mechanized transportation and a greater
prevalence of labour saving tech in home. In children these appear to be declines
in levels of physical activity due to less walking and physical education.
In both children and adults, there is an association b/w television viewing
time and the risk of obesity. A review found 63 of 73 studies 86% showed an
increased rate of childhood. Obesity with increased media exposure without
increasing proportionally to time spent watching television.
1.7.3.Factor 3: Genetics:
Obesity is actually a result of an interplay b/w genetic and environmental
factors. Polymorphisms in various genetic controlling appetite and metabolism
predispose to obesity, when sufficient food energy is present. As of 2006, more
than 41 of these sites on human genome have been linked to the development of
obesity when a favourable environment is present.
Obesity is a major feature in several syndromes, such as prader- willi
syndrome, Bardet-Biedl syndrome, Cohen syndrome and Momo syndrome. In
people with early onset severe obesity (defined by on onset before 10 years of
age and body mass index over three standard deviations & above normal 7%
harbor a single point DNA mutation).
Studies have focused on inheritance patterns rather than on specific genes
have found that 80% of the off spring of two obese parents were also obese, in
contrast to less than 10% of the off spring of 2 parents who were of normal wt ,
different people exposed to the some environment have different risk of obesity
due to their underlying genetics .
1.7.4.Factor 4: Other Illness:
Certain physical and mental illnesses and the pharmaceutical substances use to
treat them can increase risk of obesity. Medical illnesses that increases obesity
risk include several rare genetic syndrome and some congenital conditions:- hypo
thyroidism, Cushing’s syndrome, growth hormones deficiency and the eating
disorders:- binge eating disorder and night eating syndrome . The risk of over wt
and obesity is higher in patients with psychiatric disorders than in persons without
psychiatric disorder.
1.7.5.Factor 5: Social determination:
Many explanations have been put fourth for link b/w BMI and social class. In
undeveloped countries the ability to afford food, high energy expenditure with
physical labour and cultural values favouring a large body size are believe to
contribute to the obesity . A correlation in BMI change overtime has been found
among friends, siblings and spouses . Stress and perceived low social status
appear to increase risk of obesity. Smoking has a significant effect on an undivided
wt. Those who quit smoking gain an average of 4.4 kilo (9.7 lb) for men and 5
kilogram (11.0 lb) for women over 10 years. In developing world urbanization is
playing a role in increasing rate of obesity. In china overall rates of obesity are
below 5%, in some cities obesity rates greater than 20% .
1.7.6.Pathophysiology:There are many possible pathophysiological mechanism involved in the
development and maintenance of obesity. The leptin gene was discovered in 1994
and it was a satiety factor. Since leptin discovery ghrelin, insulin, orexin, pyy-3-36
and other medication have been studied.
The leptin and ghrelin are considered to be complement in their influence
on appetite with ghrelin produced by the stomach modulating short term appetite
control. Leptin is produced by a dispose tissue to signal fat storage reserves in the
body and mediates long term appetitive control.
.
For preparation of a perfect antilipidemic drug which has no side effects, we make
a formulation named as REDUCIN. In prepraration of this wt reducing
drug we consider four plants, which description is as follows:
1.8.PLANT DESCRIPTION
1.8.1. PLANT A:Cinnamomum cassia Blume:
1.8.1.1.Scientific Classification:
•
Kingdom
Plantae
•
Unranked
angiosperms
•
Unranked
magnolids
•
Order
Laurales
•
Family
Lauraceae
•
Genus
Cinnamomum
•
Species
C. Cassia
•
Binomial name
•
Cinnamomum cassia
•
Synonyms
•
Camphorina cassia (Nees + T. Nees)
•
Cinnamomum longifolium Lukman
•
Cinnamomum medium Lukman
•
Cinnamomum nitidum hook.nom.illeg
1.8.1.2.Taxonomical Enumeration:
Habitat:
Cinnamomum cassia called Chinese cassia or Chinese is an evergreen tree
originated in southern china. The tree grow to 10-15m tall, with grayish bark and hard
elongated leaves that are 10-15 cm long and have a dediedly reddish colour when young
.
Cultivation:
It is widely cultivated in Southern China and in Southern and Eastern Asia (India,
Indonesia, Laos, Malaysia, Taiwan, Thailand and Vietnam). It is one of Soul species of
cinnamomum, used for their aromatic bark, with is used as a spice. In use Chinese cassia
is the most common type of Cinnamomum used.
1.8.1.3.Medicinal uses:
Cassia bark both powdered and in whole or stick form used as a flavouring agent
for confectionary, desert, pastries and meat. It is specified in many recipies. Cassia is
sometimes added to Ceylon cinnamon but is as much tricker, coarser product. Cassia
buds resemble cloves in appearance and have a mild, flowering Cinnomon flavour. Cassia
buds are primarily used in old fashioned pickling recipies, marindas and yeast.
1.8.1.4.Chemical and biological survey :
The main component of Cassia oil are Cinnamic aldehyde, cinnamyl acetate,
benzaldehyde, dinatal and charicol, coumarin with constituents of sugar, protein, crude
fats, pectin and others. It has following biological activity, It is used as antibacterial, antiinflammatory, antidiabetic, gene expression and immune response. It also exert
antioxidant, anti-tumor, anti-thrombotic and other activities.
1.8.2.Plant B:Commiphora wightii(AM) Bhandari:
1.8.2.1.Scientific Classifications:
•
Kingdom
plantae
•
Unranked
angiosperms
•
Unranked
Eudicots
•
Unranked
rosids
•
Order
Sapindales
•
Family
Burseraceae
•
Genus
Commiphora
•
Species
C. Wightii
•
Binomial name
•
Commiphora wightii (Am) Bhandari
•
Synonyms
•
Commiphora mukul (stooks hook)
1.8.2.2.TAXONOMICAL ENUMERATION:
HABITAT:
Commiphora wightii plant may be found from Northern Africa to Central Asia but
is most common in Northern India.
Cultivation:
It is a shrub or small shrub reaching a max height of 4m within papary bark. The
branches are throny, the leaves are simple or trifoliate, the led of orate, 1-5cm long, 0.52.5cm broad, irregularly throned.
Guggul is sought for its gummy resin, in India and Pakistan guggul is cultivated
commercially. The resin of the guggul plant known as gum guggul has a fragrance similar
to treat of myrrh.
Guggul produces a resinous sap known as gum guggul. The extract of this gum
called guggullipid, which used in unani and ayurvedic medicine, a traditional unani med
for nearly 3000 yrs in India, also used for reducing obesity, rheumatoid arthritris,
osteoarthritis and sociatica . The gum guggul has a fragnance similar to that of myrrh
and is commonly used in perfumes. Guggul strengthen the neuron, often it promote
digestion and good for liver functioning, and it is antihemorrhoid in action. It also act on
urinary system help in dysurea and renal calculi. It also act as aphrodisiac agent and help
in retaining menstrual problems.
1.8.2.4.Chemical and biological survey:
It contain an oleogum resin in that contain myrcene, dimyrcene and polymyrcene.
As per constituent it has 6.9% moisture, 0.6% volatile oil, resin 61% ,gum 29.6% and
insoluble substance 3.2% beside all it also contain alkoloids in low amounts. .
1.8.3.Plant C :Emblica officinalis L:
•
Kingdom
Plantae
•
Unranked
Angiosperms
•
Unranked
Eudicots
•
Unranked
Rosids
•
Order
Malpighiales
•
Family
Phyllanthaceae
•
Tribe
Phyllanthaceae
•
Subtribe
Flueggeinae
•
Genus
Phyllantus
•
Species
P. Emblica
•
Binomial name
•
Phyllantus emblica
•
Synonyms
•
Diasperus emblica (L) Kuntze
•
Dichelactira nodicaqulis Hance
•
Emblica arborea Raf
•
Phyllanthus glomeratus
•
Phyllanthus taxifolius
1.8.3.2.TAXONOMAICAL ENUMERATION:
Habitat:
It grows in Pakistan, throughout India, Sri lanka and East to South China, West
Malaysia and Nepal, found wild in the foot hills of Himalayas and cultivated in plains.
Cultivation:
Riping in autumn, the berries are harvested by hard after climbing to upper
branches bearing the fruits.
Fruit is astringent, antipyretic, expectorant, diuretic, alterative, laxative,
refrigerant and carminative. The bark and root are astringent whereas flowers are
aparent and refrigerant. Aqeuous extract of fruit prevents the hepatotoxic and
neurotoxic effects induced by lead and aluminum in mice. The fruit has been observed
to reduce cytotoxic effects of zinc chloride, ethyl parathion and matanil yellow when
administer to mice. The seeds are regarded as aphrodisiac and antipyretic generally
Emblica officinalis fruit is used in forms of decotion, infusion of leaves and seeds,
liquour, emulsion, oil, confection, powder, paste and pickles, fruit juice with honey is
used as vermifuge and fresh fruit in the form of pickle .
Biological survey of Emblica officinalis had shown it is a rich source of vit C, a
good antioxidant, can be used as long term contraceptive, cardio protective, anticancer
and antibacterial and immune modulator. Along with improving vigor and bone strength,
it is also used for treating menstrual disorders. It also has a mild depresent action on the
CNS. It is used as oral contracepire and anti mutagenic effect .
Skin cosmetics contains powder of E. officinalis (b/c of its antioxidant properties).
It also use for improvement of brain functions for prevention and treatment of dementia
and alzheimer’s diseases. It has anticancer and antibacterial activity, use for prophylactic
treatment of migraine
and contain antistress, antioxidant, immunomodulator and
adaptogenic properties .
1.8.4.Plant D:Ferula foetida L:
•
Kingdom
Plantae
•
Unranked
Angiosperms
•
Unranked
Eudicots
•
Unranked
Asterids
•
Order
Apiales
•
Family
Apiaceae
•
Genus
Ferula L
•
Synonyms
•
Lady ginia lipsky
•
Schumannia Kuntze
•
Scorodosma Bunge
•
Soranthus Ledeb
Habitat:
Ferula is a genus of about 170 species of flowering plants in the carrot family,
native to the mediteran near region East to Central Asia. Mostly growing in arid climate.
Cultivation:
It is cultivated from East region to Central Asia. They are hebaceous perennial
plants, glowing to 1-4m tall, with stout, hollow somewhat succulent stems. The leaves
tripinnate or even more finely divided with a stout basal sheath clasping the stem. The
flowers are usually yellow, rarely white, produced in large umbels. Many plants of this
genus, are referred to as giant fennel, although they are not fennel in the strict sense.
It is used to make spice asafoetida or hira hing , the Roman called the hollow light
rod made from this plant a ferula, such rods were used for walking sticks, splints, for
stirring boiling liquids and for punishment. The led aqueous ethanol extract of ferula
foetida has shown antioxidant and antihemolytic activities. It has anti-cancer activity,
gene expression, and use in woman ailments. Also used in blood pressure, vasodilator
has effect on blood & blood vessel, it has chemotherapy usage used for lipid profile
reduction, help to protect CNS, heart, control sugar levels.
An analysis of ferula foetida describes it consist of CHO of 67.8% per kg moisture
16.0% ,proteins 4%, ,fat 11%, mineral 7.0% and fiber 4.4%. Its mineral and vitamin
content include substantial calcium besides phosphorus ion, carotene, riboflavin and
niacin. Its clarific value is 297, contains 40.64% resinous material comprised of ferulic
acid, umbeliferone , asaresinotannols, fernesiferols A, B and C .
CHAPTER .2: GENERAL INTRODUCTION
The use of herbs as medicine is the best oldest remedy of health care,and
one known to humanity and has been used in all cultural, throughout history.
Early humans recognized their dependence on nature for a healthy life and since
that time humanity has depended on the diversity of plant resources for food,
shelter and medicines to cure myriads of ailments. Led by instinact taste and
experience, men and women previously treated illness by using plants, animal
parts and minerals treated illness.
A herb is a plant or a part of a plant valued for its medicinal aromatic or
saromy qualities. Herbs can be viewed as biosynthetic chemical in laboratories,
producing a no. of chemical compounds, herbal remedies or medicines consist of
portion of plants of unpurfieid plant extracts cotntaining several constituents,
which often work together synergistically. Herbal medicine or herbalism is the use
of herbs or herbal products for their therapeutic or medicinal value. They may
came from leaves, roots, bark, seeds and flowers. Chemicals known to have
medicinal benefits are referred to as active ingredients.
A/c to WHO(1996 a and b, 1992), standardization and quality control of herbs is
the process involved in the physiochemical evaluation of crude drug covering
aspects such as selection and handling of crude drug, safety, efficiency and
stability and amount of finished product. Alteration is normally paid to such
quality parameters such as:
2.1.Parameters for Crude Drug Evaluation:
Macro and Microscopic Examination: (for identification of right variety).
Foreign Organic Matter: This involves removal of matter other than source
plant to get the drug in pure form.
Ash values: These are criteria to judge the identity and purity of crude drug.
Total ash, sulphate & ash, water soluble and acid in soluble ash etc.
Moisture Content: checking moisture content helps to reduce error in the
estimation of the actual no of drug material, low moisture suggest better stability
against degradation of product.
Extractive Value: These are indicative wts of the extractable chemical
constituent’s crude drug under diff. solvent environment.
Crude Fibre: This help to determine the woody material component and it is a
criteria for judging purity.
2.1.2.Qualitative Chemical Evaluation:
This covers identification and characterization of crude drug with respect to
phytochemical constituents. It employs different analytical tech to detect and
isolate the active constituent. Phytochemical screening technique are involve
botanical identification, extraction with suitable solvent, purification and
characterization of the active constituent of pharmaceuticals importance.
•
Chromatographic Examination: include identification of crude drug
based on the use of major chemical constituent.
•
Qualitative Chemical Evaluation: To estimate the amount of the major
classes of constituents.
•
Toxicological Studies: This helps to determine the pesticides, potentially
toxic elements, safety studies in animals like LD50 and microbial among to establish
the absence or presence of potentially harmful organism.
2.2. IDENTIFICATION OF PLANTS:
2.2.PLANT A:
2.2.1.1.ORGANOLEPTIC EVALUATION OF PLANT A:
a)Macroscopic Evaluation:
•
Bark about 0.5 mm thick,brittle,occur as single or double.
•
Closely packed compound quills up to a meter or more in length and about km
in diameter.
•
Outer surface is dull yellowish brown,marked with pale waxy longitudinal lines
with occasional small holes.
•
Inner surface dark in colour,strated with longitudinally elongated reticulation.
•
fracture-splintery
•
Odour-fragment
•
Taste-sweet,aromatic with sensation of warmth.
b) Identity, purity and strength:
•
Foreign matter → not more than 2%.
•
Total ash → not more than 3%.
•
Acid insoluble → not more than 2%.
•
Alcohol soluble extraction not less than 2%.
•
Water soluble extraction not less than 3%.
•
Volatile oil not more than 1%.
c) Constituents:
•
Essential oil, tannins and mucilage .
2.2.1.3.POWDER MICROSCOPY OF PLANT A:
Diagnostic features
Explanations
•
Stone Cells
Stone cells are occassionally found.
•
Paranchymatous cells
Paranchymatous cells are found.
•
Phloem
Phloem fibers has thick wall.
•
Starch grains
Starch grains small in quality.
•
Ca- oxalate
Minute occular crystal of caoxalate found.
•
Medullary rays
are of isodiametric cells.
2.2.1.4.HISTOLOGY OF PLANT A:
Transverse section of bark, devoid of cork and cortex show except at certain places.
•
Oxalate present.
•
Paricyclic sclerychyma.
•
3 or 4 rows of isodiametric cells.
•
Starch grains.
•
Small gps of pericyclic fibers embeded at intervals in the sclernchyma.
•
Phloem of tangential band of tissues altering with parenchyma and containing
axillary elongated secretary cells.
•
Secretary cells containing volatile oiler mucilage.
•
Phloem fibers with thick wall isolated in short tangential rows.
•
Medullay ray of isodiametric cells, mostly 2 cells wides.Corticle, parenchyma and
medullary ray containing small starch grains, minute a circular crystals of Calcium.
•
•
2.2.2.PLANT B:
Leaves and Flowers of Plant B
Gum of Commiphora wightii
2.2.2.1.ORGANOLEPTIC EVALUATION OF PLANT B:
a)Macroscopic evalution:
•
It is translucent, tears of varying sizes.
•
Reddish yellow or brown in colour more often in resinous lump when the darker in
colour on long storage.
•
Fracture is brittle.
•
Exposing a rough or waxy surface having moist uncutanious appearance.
•
Odour is bashmic
•
Taste is Bitter, acrid, aromatic
•
Makes milky emulsion in hot water and easily burn when fresh, viscid and golden
colour.
b) Identity, purity and strength:
•
Foreign matter not more than 4%.
•
Total ash not more than 5%.
•
Acid insoluble ash not more than 1%.
•
•
•
Volatile oil not more than 1 %.
c) Constituents:
•
Essential oil, gum, resin, steroids.
2.2.2.3. Powder Microscopy of Plant B:
Diagnostic features
Explanations
•
Spiral vessels
the spiral vessels found abundant.
•
Starch grain
starch grain are oval like in shape.
•
Stone cells
stone cells of diff. shapes are found.
•
Cork
There was cork in surface view.
•
Isolated scleroids
isolated scleroids of rob like shape.
•
Fibers
longitudinal fibers found in microscopy.
2.2.2.4.Histology of Plant B:
Transverse section of the Plant B shows:
•
A daxial epidermis: A large vascular bundle of adaxial epidermis.
•
Hypodermis:
•
Parenchyma: Spongy, few oleo resin located.
•
Midrib: Midrib with vascular bundle found.
•
Collenchyma: Mid rib count of thin 20mm of collenchymas.
•
Secretary ducts: Oleoresin ducts are covered by small rectangular
Consist of single layer of coloumnar plasades.
parenchymatous epithelium cells.
•
Xylem: Xylem shows, situated towards.
•
Phloem: Phloem situated upwards.
2.2.3:PLANT C:
2.2.3.1.ORGANOLEPTIC EVALUATION OF PLANT C:
a)MACROSCOPIC EVALUATION:
•
Macroscopic evaluation shows heavily wrinkled fruit deep impression in the center
having net like appearence.
•
Has internally triangular strong seed having sharp margin with 3 stiff fibers.
•
Texture is rough.
•
Fracture is hard.
•
Shape somewhat reni form.
•
Size is 2 – 3 cm.
•
Colour is blackish and dusty.
•
Odour is sweet & sour
•
Taste is sour or slightly acidic.
b)Identity purity and strength:
•
Foreign mater not more than 3%.
•
•
•
•
c) Constituents:
Ascorbic acid and gallotannins.
2.2.3.3:Powder Microscopy of Plant C:
Diagnostic features
Explanations
•
Ca - oxalate
Cubical shape ca-oxalate are most frequently found.
•
Phloem
Heavy group of phloem fibers observed.
•
Tannin Cells
Thick deposition of hydrolysalide tannin in hexagonal cell.
•
Stone Cell
Narrow luman stone cells also seen.
•
Starch grain
Simple, small, rounded starch grains were abundant.
•
Single phloem fiber
Single strand were found which rich in nos.
•
Epidermal cells
epidermal cells in a big fragment which are centrally empty.
•
Lignified and bast
Rows of lignified cells found along with bast cells.
•
Cortical cells
thin walled oval chain like cortical cells are found.
2.2.3.4:Histology of Plant C:
•
Diagnostic features
Explanations
•
Cuticle
Most prominent out most layer of the section having sunken
stomata.
•
Epidermis
Layers of barrel shape cell last beneath the stomata.
•
Cortical region
Composition of parenchyma cells in cortical region.
•
Cortical cells
thickly lignified rounded cells are occupied 3-5 layers in the
cortical region.
•
Ca-oxalate
Cubical Ca-oxalate are scattered in the section especially in
cortical region.
•
Phloem vessels
corticle region.
thin elongated phloem fibers are arranged in a group under the
•
2.2.4:PLANT D
2.2.4.1. ORGANOLEPTIC EVALUATION OF PLANT D:
a)Macroscopic evaluation of Plant D:
•
Rounded, flatttened or masses of agglutinated tears.
•
Grayish white to dull yellow.
•
Mostly 12-25 mm in diameter, 1-4m tall.
•
Freshly exposed surface yellowish and translucent or milky white.
•
Opaque.
•
Slowly become finally reddish brown.
•
Odour is strong.
•
Taste: bitter and acrid
•
Stout hollow, succulent stems.
b)Identity purity and strength:
•
Foreign mater not more than 2%.
•
•
•
•
c) Constituents:
It contains 40.64% resinous material comprised of ferulic acid, umbeliferone ,
asaresinotannols, fernesiferols A,B and C.
2.2.4.3. Identification Tests:
•
Freshly broken surface when touched with sulphuric acid, reddish brown colour
produced changes to violet.
•
Boil 0.2 gm with 2ml of HCl acid for about 1min, cool and dilute with an equal amout
of water and filter to 3ml of dilutes, chromic florescene is produced.
•
Titrate with H2O → Milky white
•
Treatment with 50% nitric acid → Green Colour.
•
Treatment with fractured dark surface with H2SO4 → Reddish Brown
•
Combined umbeliferone → Dark Blue Colour.
•
On burning → Yellow Flame
2.2.5.1. Powder Microscopy of REDUCIN:
Diagnostic features
•
Stone Cells
explanations
Rounded rhombohedral shaped stone
cells are found.
•
Fibers
Elongated fibers of two types, phloem
and lignified.
•
Oil Cells
Thin and thick walled almost oral in
shape.
•
Ca - oxalate
various types, Ca- oxalates are found.
•
Tannin Cells
Thick deposition of hydrolysalide tannin
in hexagonal cells.
•
Mucilage cell
Most of the spherical shapes cell contain
mucilage.
•
Starch grain
Simple type of starch grain found.
•
sclerieds
Thickly lignified fibers.
CHAPTER 3
3. EXPERIMENTAL STUDIES:
The phytochemical and pharmacological work was performed at Research Institute of
Pharmaceuticals Sciences, Department of Pharmacognosy, Faculty of Pharmacy, and
University of Karachi.
3.1. Apparatus:
Following apparatus were used for experimental purpose:
•
Rotary Evaporator
Eyela (Japan) was used for extraction and evaporation of the solvent from the extract
under reduced pressure and controlled temperature.
•
Lyophilizer
Freeze dryer model FDI, (Eyela, Tokoio Rikakekai Co. Ltd. Japan) was used for the
removal of water from the extract under controlled temperature.
•
Electronic Microscope
Laboval-4, Germany, was used in microscopic examination of plants powder.
•
Stereomicroscope
(Wolfe, Carolina, 59.18.18, Burlington, North Carolina 2715) was used for
organoleptic evaluation of plant drugs in a magnified from.
•
Ultraviolet Lamp
(Max 254 and 366) was used for the detection of chromatographic plates (for
suspected chromophores in chemical constituents)
•
Water Bath
Thermostatic water bath Model No. HH. S21.8, (Jiangsu Medical Instrument Factory
China) was used to maintain the temperature.
•
Physical Balance
Below mentioned physical balance were used for weighing extracts during
experiments.
•
Libro AEG – 120 Shimadzu (Japan)
•
Libro EB – 3200D, Shimadzu (Japan)
•
Grinder
West point automatic series TSK-333 France (National) was used for grinding of
herbs.
3.2. MATERIAL AND METHODS:
For Chromatographic Procedures
Silica Gel for TLC Plate
•
20x20 cm silica gel 60 florescence at 254 nm (Merck, Germany).
•
5x10cm gel 60T (0.2mm thick) pre coated TLC plates, florescence at 254nm
(Merck, Germany).
•
Pre coated Silica gel F254 TLC plate (E-Merck) was used to check the purity of
compounds.
Rotary evaporator
The following materials were used for chemical work during experiments.
•
Plant material (about 2,000gm of each plant A-D) were purchased and collected from
the standard shop of herbal market (address given in chapter II) and were identified
by Prof. Dr. Ghazala H. Rizwani, Chairperson Department of Pharmacognosy, Faculty
of Pharmacy, University of Karachi. Specimen bottles of the plants (0040, 0041, 0042,
and 0043 for plant drugs A-D respectively) were deposited in the Pharmacognosy
Herbal Museum, Department of Pharmacognosy, and University of Karachi.
•
For checking the solubility of drugs in different reagents by color reaction; lead
acetate, ferric chloride, n-hexane, and Iodine solution were obtained from Merck,
Germany / BDH, UK.
3.3.Solvents:
•
N-Hexane (Merck, Germany)
•
Methanol (Merck, Germany)
•
Ethyl acetate (Merck, Germany)
•
Chloroform (Merck, Germany)
•
Ether (Merck, Germany)
•
N-Butanol (Merck, Germany)
•
Acetone (Merck, Germany)
•
Ferric chloride (Merck, Germany)
•
Lead acetate (Merck, Germany)
•
Iodine solution (Merck, Germany)
•
Sulphuric acid (Merck, Germany)
•
Hydrochloric acid (Merck, Germany)
•
Nitric acid (Merck, Germany)
•
Distilled water
3.3.1. Solvents systems Used in Chromatography:
Following solvent systems were used for chromatography:
•
Ethyl Acetate – Methanol – Water (9:1:0:1)
•
Hexane (100%)
•
Hexane – Chloroform (7:3)
•
Chloroform (100%) – Water 9:1)
•
Chloroform – Methanol – Water (8:2:0.2)
•
Butanol – Ethanol – Water (8:2:0.2)
TABLE 1
3.4.1.Behaviour of powder with different Chemical regents
(Plant B)
S.No.
Treatment
Observation
1
Powder + 1 N NaOH
Yellowish brown
2
Powder + Saturated Sulphuric acid
Yellowish green
3
Powder + Acetic acid
Orange yellow
4
Powder + Conc. Hcl.
Reddish brown
5
Powder + Conc. HNo3
Chocolate brown
6
Powder + Iodine (5%)
Blackish brown
7
Powder + Sakuwabiff’s Reagent
Yellowish brown
8
Powder + Ferric chloride (5%)
Dark Blackish brown
9
Powder + 40% NaOH+Few drops of 10%
Blackish brown
Lead acetate
10
Powder + Sudan III (ALCHOHOLIC)
Dark reddish orange
11
Powder + Conc. HNo3 + Ammonia
Yellowish orange
12
Powder + 35% HCI
Brownish
13
Powder + 5% KOH
Yellowish green
14
Powder + Phloroglucinol: HCI (1:1)
Yellowish brown with purple spots
TABLE 2
3.4.2Behavior of powder with different Chemical
Reagents {Plant C}
S.No.
Treatment
Observation
1
Powder + Iodine sol
Dark brown
2
Powder + Chloroform
Light Brown
3
Powder + Hexane
Very Light Brown
4
Powder + Methanol
Light brown
5
Powder + Acetone
Light brown
6
Powder + Ferric Chloride
Bluish Black
7
Powder + Lead Acetate
White ppt with clear sol
TABLE 3
3.4.3. Behavior of powder with differencial reagent
(Plant D)
S.No.
Treatment
Observation
1
Powder + H2O
Milky White
2
Powder + 50% nitric acid
Green
3
Powder + H2SO4
Dark Reddish Brown
4
Powder + Umbeliferone
Dark blue
5
Powder on burning
Yellow Flame
3.5.Phytochemical Analysis for Primary &
Secondary Metebolites of Plant A-D:
TABLE 4
3.5.1:Phytochemical Analysis of Plant A
Tests
Carbohydrates :
Molish test
Fehling test
Proteins :
Biuret test
Steroids :
Salkowski test
Alkaloids:
Dragendorff’s
Saponin test:
Froth test
Glycosides test:
Legal’s test (for
cardenoloids)
Lekellar killani test
Starch:
Tannic acid test
Flavanoids :
Shinoda test
Tannins &Phenols:
FeCI3 test
Reagents
Conc. Hcl
Conc Hcl+Mg turnnings
4% NaOH, 1% CuSO4
Chloroform and conc. H2SO4
Positive result
violet ring
yellow and red ppt
Violet or pink color
Chloroform layer appeared red
and acid layer show greenish
yellow inflorescence
Dragendorff’s regt.
Orange ppt.
H2O
Honeycomb froth
Pyridine, Sodiumnitroprusside
Pink to red color.
Reddish brown color &bluish
green color
Glacial acetic acid, 5% FeCI3
20% Tannic acid
White ppt
95% ethanol, HCI,
Magnesium
Pink Color
FeCI3
Intense green colour
TABLE 5
3.5.2:Phytochemical Analysis of Plant B
Tests
ALKALOIDS :
Mayers Test
Wagners Reagent
FLAVONOIDS:
NaoH and HCL TEST
H2SO4 TEST
PROTEIN:
Milton Test
Ninhydrin Test
Reagents
1.36 gm Mercuric Chloride
5gm of Potaasium Iodide
Positive result
Cream Colour PPT
1.27 gm of iodine and 2g of
Potassium Iodine
+VE
NaoH and HCL
H2SO4
Yellow Orange colour
Orange colour
2 ml of milton reagent
2 ml of ninhydrin
White Colour
Blue+Purple colour
TANNINS:
10%of lead acetate
Lead Acetate
STEROIDS:
Libermanburchard test 2-3 ml of acetic anhydrate
glacial acid+2 drops of
H2SO4
White Colour PPT
Bluish green colour
TABLE 6
3.5.3:Phytochemical Analysis Of Plant C
Tests
Carbohydrates :
Molish test
Fehling test
Reagents
Few drops of alcohalic alpha
nephtohol+2ml of conc
sulfuric acid
Positive result
violet ring
fehling sol
Brick Red PPT
Bendict reagent
Brown PPT
GLYCOSIDES:
Legals test
sod.nitroprusside+sod hydroxide
Colour Change
Libermanburchard
test
Libermanburchard reagent
Bendict test
Fixed oils:
Spot test
Sponification test
Colour change
oil statin
Sample press b/w two filter
papers
pot.hydroxide+phenolpthalei sponification indicated
n
Alkaloids:
Dragendorff’s
Brown colour
Mayers test
mayers reagent
cream colour
Wagner test
wagners reagent
Reddish Brown
PROTEIN:
Ninhydrin test
Miltons test
Tannins:
FeCI3 test
Ninhydrin reagent
Miltons reagent
Blue
White
FeCI3
Intense green colour
TABLE 7
3.5.4:Phyochemical Analysis of Plant D
Tests
Carbohydrates :
Molish test
Fehling test
Proteins :
Biuret test
Steroids :
Salkowski test
Alkaloids:
Dragendorff’s
Saponin test:
Froth test
Glycosides test:
Legal’s test (for
cardenoloids)
Lekellar killani test
Starch:
Tannic acid test
Flavanoids :
Shinoda test
Tannins &Phenols:
FeCI3 test
Reagents
Positive result
Conc. hcl
Conc hcl+mag turnnings
Absent
4% NaOH, 1% CuSO4
Absent
Chloroform and conc. H2SO4
Absent
Brown colour
H2O
Absent
Pyridine, Sodiumnitroprusside
Absent
Glacial acetic acid, 5% FeCI3
Absent
Absent
20% Tannic acid
Absent
95% ethanol, HCI,
Magnesium
Absent
FeCI3
Absent
3.6. Extraction and Isolation Procedures:
3.6.1: Extraction and Isolation of Reducin Powder:
For the extraction of REDUCIN powder, dry drugs of all four plants (i.e. Plant A,B,C
and D; approximately 2,000gm each) were first cleaned, garbled, washed with
clean water and when dried (separately). Then the dried materials of plant drugs
were grinded in to coarse powder with the help of a grinder.
After getting coarse powder (about 7kg) of all plant drugs, about 2kg was kept for
getting the individual MeOH extract of plant drugs for phytochemical and
chromogenic testing of all plant drugs respectively; whereas remaining 5kg was
mixed well and then grinded again to again fine powder of REDUCIN .This fine
powder was percolated in 80% methanol at room temperature for 15 days. The
percolate was then filtered through Whatman Filter Paper No.1.
This process was repeated for three times. The methanolic extract of REDUCIN
was then evaporated under reduced pressure and controlled temperature at
400C.A reddish brown gummy residue was obtained, which was then lyophilized
and finally we obtained brown powder of REDUCIN about 4kg powder was kept
for clinical studies, whereas about 1kg powder was kept for comparative
chromatographic analysis of all plant drugs .
3.6.2: Extraction of Plant Drugs (A-D) for Phytochemical
and Chromogenic Testing:
Same procedure was adopted for extraction of all plant drugs (i.e. Plant A,B,C, and
D). The plant drugs (about 2kg) were first cleaned, garbled, washed with clean
water and then dried. Then the dried materials of plant drugs were grinded in to
coarse powder with the help of grinder.
The coarse powder of plant drugs were percolated in 80% Methanol for 15 days at
room temperature separately. The percolate was then filtered through Whatman
Filter Paper. No.1. This process was repeated for three times, and finally we got
first methanolic extract of all plant drugs. This extract was evaporated under
reduced pressure and controlled temperature at 400C to get second extract, which
was then again reconstituted in methanol to get the third extract. The third
extract was lastly used for phytochemical and chromogenic testing of individual
plant drugs.
3.6.3:Chromatogram Development for TLC
Chromatography:
The methanolic extracts (of reducin and individual plant drugs) so obtained were
analyzed on TLC plates by using different solvent systems. These plates were first
observed under ultraviolet lamp at wavelength of 254 nm and 366nm. Then the
iodine vapors were used (the chromatogram was introduced in to a closed vessel
on the bottom of which some crystals of iodine have been placed) for making
unstable complexes with the compounds for identification purposes.
Afterwards Ceric Ammonium Sulphate reagent, Dragondroff’s reagent were used
for the detection of chemical compounds of different nature found in the
methanolic fraction of plant drugs and compared them with Reducin fraction.
CHAPTER 4
4. CLINICAL STUDIES OF REDUCIN:
4.1. Introduction:
In 2012, the U.S. Preventive Services Task Force (USPSTF) issued the recommendation
that all adults be screened for obesity, and that patients with a body mass index (BMI) of
30 kg/m2 or greater be offered intensive, multi-component behavioral interventions. The
American Academy of Family Physicians has endorsed the USPSTF recommendation,
which is based on evidence that intensive counseling can promote modest sustained
weight loss and improved clinical outcomes.
The prevalence of obesity exceeds 30% in adults and is associated with increased risk of
such serious health problems as cardiovascular disease, type 2 diabetes, and various types
of cancer. These co morbid conditions are associated with greater use of health care
services among obese patients.
Obesity is also associated with an increased risk of premature death in adults younger
than 65.
4.1.1:Consequences of Obesity
Physical
Psychosocial
Functional
Cancer
Depression
Absenteeism from school
Cardiovascular disease
Discrimination
or work
Cholestasis
Low self-esteem
Disability
Dyslipidemia
Negative body image
Disqualification from
Gallbladder disease
Negative stereotyping
active military/fire/ police
Glucose intolerance and
Social marginalization
services
insulin resistance
Stigma
Low physical fitness
Hepatic steatosis
Teasing and bullying
Mobility limitations
Hypertension
Reduced academic
Hyperuricemia and gout
performance
Menstrual abnormalities
Reduced productive
Orthopedic problems
Unemployment
Reduction of cerebral
blood flow
Sleep apnea
Type 2 diabetes
4.1.2. Screening and Diagnosis:
BMI is recommended for use in clinical practice as a practical way to identify
individuals who are overweight or obese. Furthermore, calculating BMI is still a good
way to evaluate changes over time, because incremental increases most likely represent
gains in body fat.
Recognizing that BMI is just one indicator of potential health risks associated with being
overweight or obese, the National Heart, Lung and Blood Institute (NHLBI) recommends
that physicians also look at the following factors,
•
Risk factors for diseases associated with obesity, such as high blood pressure and
physical inactivity.
•
Waist circumference as a measure of abdominal adiposity
4.1.3.Waist Circumference:
Abdominal adiposity is an important independent risk factor for cardiovascular disease,
type 2 diabetes, dyslipidemia, and hypertension. The NHLBI defines abdominal obesity
as
•
Waist circumference greater than 40 in (102 cm) in men
•
Waist circumference greater than 35 in (88 cm) in women
Individuals with larger waist circumferences have more than a fivefold greater risk
of multiple cardio metabolic risk factors, even after adjusting for BMI, compared with
individuals with waist measurements in the normal range
4.1.4.Medications That Promote Weight Gain
Anticonvulsants
Antihypertensives Antipsy
hotics
Valproic acid
Clonidine
Chlorpro
Corticosteroid
s
Psychotropics
mazine
Carbamazepine
Guanabenz
Thiothixene
Lithium
Antidepressants
Methyldopa
Haloperidol
Sulfonylureas
Amitriptyline
Prazosin
Olanzapine
Glipizide
Imipramine
Terazosin
Clozapine
Glyburide
Phenelzine
Propranolol
Risperidone
Nisoldipine
Quetiapine
Abdominal obesity is also one of five diagnostic criteria for metabolic syndrome.
Approximately 34% of adults meet the criteria for metabolic syndrome, and the risk
increases with age. Men ages 60 years or older are more than four times as likely and
women ages 60 years and older are more than six times as likely to be diagnosed with
metabolic syndrome compared with younger adults (ages 20 to 39 years
4.1.5: Classification of Overweight and Obesity, and
Associated Disease Risk:
Disease Risk (Relative to Normal Weight
and Waist Circumference)t
Classification*
BMI
Obesity Waist
Waist
(kg/m2)
Stage
Circumference
Circumference
Men: <40 in (102)
Men: >40 in (102
cm)
cm)
Women: <35 in (88 Women: >35 in (88
cm)
cm)
Underweight
<18.5
-
-
-
Normal
18.5 to 24.9
-
-
-
Overweight
25.0 to 29.9
-
Increased
High
Obesity
30.0 to 34.9
I
High
Very high
35.0 to 39.9
II
Very high
Very high
40.0
III
Extremely high
Extremely high
Extreme obesity
4.1.6: Metabolic Syndrome:
Metabolic syndrome is a constellation of risk factors, including abdominal obesity,
atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose levels,
that increase the risk of cardiovascular disease.
The predominant underlying risk factors for metabolic syndrome are abdominal
obesity and insulin resistance. Although many patients may be genetically susceptible to
metabolic syndrome, it rarely develops in the absence of obesity and physical inactivity
4.1.6.1: Diagnostic Criteria for Metabolic Syndrome:
Measure (any 3 of 5 criteria
constitute diagnosis of
metabolic syndrome)
Categorical Cut Points
Elevated waist circumference
>102 cm (>40 in ) in men
>88 cm (>35 in) in women
Elevated TG
>150 mg/dL (1.7 mmol/L)
or drug treatment for elevated TG
Reduced HDL-C
<40 mg/dL (1.03 mmol/L) in men
<50 mg/dL (1.3 mmol/L) in women
or drug treatment for reduced HDL-C
Elevated BP
>130 mm Hg systolic
>85 mm Hg diastolic
Elevated fasting glucose{or
treatment for elevated fasting
glucose}
or drug treatment for hypertension
>100mg/dl{5.6mmol/L},or drug
treatment for elevated glucose.
4.2: Management of Obesity:
4.2.1:The 5 A's for Evaluation and Treatment of Obesity:
Assess
Severity of obesity with calculated BMI, waist circumference, and
comorbidities Food intake and physical activity in context of health
risks and appropriate dietary approach Medications that affect
weight or satiety
Readiness to change behavior and stage of change.
Diagnosis
Advise
of
overweight,
obese,
or
severe
obesity
Caloric deficit needed for weight loss Various types of diets that
lead to weight loss and ease of adherence Appropriateness, cost, and
effectiveness of meal replacements, dietary supplements, over-thecounter weight aids, medications, surgery Importance of selfmonitoring
Agree
If patient is not ready, discuss at another visit. If patient is motivated
and ready to change, develop treatment plan. If patient chooses diet,
physical activity, and/or medication, set weight-loss goal at 100/0
from baseline. If patient is a potential candidate for surgery, review
options
Assist
Provide a diet plan, physical activity guide, and behaviormodification guide. Provide Web resources based on patient interest
and need Identify method for self-monitoring (e.g., diary) Review
food and activity diary on follow-up (reassess if initial goal is not
met)
Arrange
Follow-up appointments to meet patient needs Referral to registered
dietitian
and/or
behavioral
specialist
for
individual
counseling/monitoring or weight-management class Referral to
surgical program Maintenance counseling to prevent relapse or
weight regain
4.2.2: Pharmacotherapy:
Drug
Mechanism of Action
Possible Adverse Effects
Lorcaserin (Belviq)
Decreases appetite,
Headache, dizziness, fatigue, nausea,
Orlistat (Xenical)
increases
dry mouth, constipation
Phentermine and
feeling of fullness,
Intestinal cramps, gas, diarrhea, oily
topi
Blocks absorption of fat,
spotting.
ramate extended-
Decreases appetite,
Increased heart rate, birth defects,
release (Qsymia)
increases
tingling of hands and feet, insomnia,
feeling of fullness
izziness, constipation, dry mouth
4.2.3: Bariatric Surgery:
Bariatric surgery may be considered in adults who have not achieved weight loss
with dietary or other treatments and who have a BMI of 40 kg/m2 or greater, or for those
who have a BMI of 35 kg/m2 or greater with significant obesity-related comorbidities
(e.g., severe hypertension, type 2 diabetes, obstructive sleep apnea).Bariatric surgery may
also benefit patients with obesity-related comorbidities who have a BMI of 35 kg/m2 or
lower, but it is not routinely recommended for these patients
4.3: Clinical Studies of Reducin:4.3.1: Proven Therapeutic Efficiency of Herbal Drugs
(A-D) in Literature:4.3.1.1:Plant A:- (Cimamomum cassia blume):
Cinnamomum cassia blume have a direct role in lipid metabolism and
prevent hyper cholesterolemia and hyperlipidemia and lower free fatty acid by its
strong lipolytic activity. Dietry cinnamate inhibits the hepatic HMG COA
reductase activity resulting in lower hepatic cholesterol-content. Suppress lipid
preoxidation via enhancement of hepatic antioxidant activity.Cinnamomum cassia
may have an effect on treating hyper lipidemia and there may be responsible for
the prevention of consequences of aging process, from hypertension to heart
failure, cardiovascular disease and myocardial infarction.
4.3.1.2:Plant B:- (Commiphora wightii):
Guggul an oleogum resin is plant exudates of Commiphora wightii, has been
use medicinally since vesdic period for treatment of no of diseases such as hyper
cholesterolemia, artherosclerosis, obesity, liver disorders, digestive problem and
menstural irregulaties. Guggul of Commiphora wightii possess lipid lowering
effect, in various studies it has shown to decrease atherosclerosis, lower serum
cholesterol and triglycerides and also decrease HDL and cholesterol.
4.3.1.3:Plant C:- [Embelica officinalis):
Although Embelica officinalis does not have a direct effect on reproductive
organs but it exhibits effects on total body hormonal system. Some effects are:It is nutritional power house and used to boost immunity and restore body
immunity, provides energy to vital organs and used in chronic illness recovery.
Its help in regulating blood glucose level in diabetic pts, improve hb level
and is an imperative eye and liver toner.
It possess ant inflammatory action and in various GIT inflammation such as
gastritis, it has been used. It contains natural digestion enzyme and therefore used
in indigestion. It lowers serum cholesterol and reduce body heat / wt naturally.
4.3.1.4:Plant D:- (Ferule foetida):
Ferule foetida used to make spice as asafoetida or hing. It has many
marvelous effects on the human body. Which are:It has ant-oxidant, anti-hemolytic activity. It has anticancer activity, gene
expression, use in women ailments. It is also used in blood pressure, vasodilator,
has effect on blood & blood vessels. It has chemotherapy usage, used for lipid
profile reduction, help to protect CNS & Heart. It also control blood sugar levels.
4.3.2:Animal trials:
4.3.2.1:Aims and objectives:By conducting these trials, our main objective to establish the incidence of
obesity in pts with high T.Gs levels, to assess the age and severity of obesity and to
establish the efficacy of formulated drug with in the pts presented with obesity
problem.
4.3.1.2:Conduction and Evaluation of studies:
The research was conducted and evaluated by the ethical committee of
Dr. Zia Uddin hospital Block B, North Nazimabad and Murshid Hospital and
health care center hub-river road Karachi.
•
Participants:
The study was performed on total nos of 30 adult long Evans (Rattus Rattus)
rats weighing b/w 200 to 210 gm collected from pharmacology Dept of SON of
Murshid Hospital. The chosen animals were housed in cages separately at normal
atmospheric temp b/w 25 to 290 C, under good ventilation and were given water &
standard balanced diet. Animals were randomly distributed in to 4 gps each cage
was labeled for identification of different gps.
4.3.1.3:Trial 1:
Trial 1 was conducted to demonstrate the effect of Reducin on normal adult
male rats, for this purpose a total no of 12 rats were taken and was divided in to
two gps, six animals in each gp.
•
GP A:
Each animal received laboratory diet 20g/day and distilled water for 35 days.
•
GP B:
Each animal receive 15% powder of Reducin mixed with laboratory diet
/day for 35 days.
4.3.1.4:Trial II:
Trial II was conducted to demonstrate the effect of Reducin on hyper
cholestrolemic rats. For this purpose a total no of 18 rats were taken and divided in
to 3 gps containing 6 animals in each gp.
•
GP C:
Hypercholestrolemic gp that received fatty mixture diet (normal lab diet plus
1% cholesterol with 0.3% cholic acid) for 35 days.
•
GP D:
This gp receive fatty mixture diet with 15% of powder of Reducin for 35
days.
•
Collection of Blood Specimens:
The rats were kept fasted over night before taking the blood samples. All the
animals were anesthetized with diethyl ether and blood samples were collected in
test tubes and allow to coagulate at room temp. It was then centrifuged at 3000 rpm
for 30 min in a centrifuge machine. The clear non hemolysed supernatant sera was
quickly removed and stored at -200C for biochemical analysis of serum lipid
profile at the murshid hospital laboratory.
•
Biochemical Analysis:
After collection of all blood & specimens, serum total cholesterol (TC),
serum high density lipoprotein cholesterol (HDL-C) and serum triglycerides (TGS)
were measured by enzymatic calorimetric (CHOD-PAP) method. Low density
lipoprotein cholesterol (LDL-C) was calculated by frie dewards formula.
•
Statistical Analysis:
The data were analyzed using unpaired t test. Results were expressed as
meant ± SE and p value <0.05 and <0.01 were considered statistically significant
and highly significant especially.
4.3.1.5:Results:
Table shows the effect of Reducin on serum lipid profile of adult male rats.
Serum total cholesterol, serum LDL cholesterol, HDL cholesterol and serum
triglycerides level shows some difference b/w the Reducin gp (B) and the control
gp (gpA).
4.3.2.5.1: Effects of Reducin on Serum lipid Profile of
Adult Male Rats (AV/SB):
Parameters
GPA
GPB
N=6 mean ± SE
N=6 mean ± SE
71.17 ± 1.59
69.83±3.04
>0.05
Serum TG (mg/dl)
78.10 ± 2.45
76.33±1.93
>0.05
Serum HDL
31.50±93
30.67±4.87
>0.05
Serum total
P value
Cholesterol mg/dl
Cholesterol mg/dl
Serum LDL
26.61±2.23
23.90±6.00
>0.05
4.3.2.5.2:Effects of Fatty Mixture Feeding Diet on
Serum Male Rats [A V/S C]:
Parameters
Group A (n=6)
Group B (n=6)
Mean ± SE
Mean ± SE
serum total
cholesterol
P VALUE
136 ±3.74
<0.01
78.1+2.45
106.5 ± 2.85
<0.01
31.50 ± 0.93
30.81 ± 2.73
>0.05
76.61 ± 2.23
83.81 ± 5.6
>0.05
71.17 +1.59
[mg/ml]
Serum T.G
(mg/dl)
Serum HDL
Cholesterol
(mg/dl)
Serum LDL
Cholesterol
(mg dl)
4.3.2.5.3: Effects of Reducin on Serum lipid profile of
adult male rats fed with fatty mixture diet (C V/S D):
Parameters
Serum total
GPC
GPD
N=6 mean ± SE
N=6 mean ± SE
136 ± 3.74
119.5±2.68
P value
<0.01
Cholesterol mg/dl
Serum TG (mg/dl)
106.5 ± 2.85
92.13±3.02
<0.01
Serum HDL
30.81±2.78
29.17±1.73
>0.05
83.81±5.61
71.91±1.88
Cholesterol mg/dl
Serum LDL
<0.05
4.3.2.6:Discussion:
A proving body of research demonstrated that the commonly used herbs &
spices such as garlic, cumin, cloves cinnamomum, thyme, guggul, fine spices, bay
leaves, hing, amla can be used therapeutically in some cases.
Medicinal plants play a vital role for the development of new drugs. Almost
70% modern medicines in Asia are derived from natural products. Medicinal plants
play a central role not only as traditional medicines but also as trade commodities,
mentioned the demand of distant markets.
In experiments I & II all conventionally measured indicators (serum
cholesterol, T.G, LDL and HDL levels) of lipid profile were slightly arranged in gp
B as compare to these in control gp A.
In trial II the effect of Reducin was observed on serum lipid profile of
hyperlipidemia in long Evan rats on describing the fatty diet gp showed significant
increase in serum lipid profile parameters of (T.C, T.G, LDLC) as compared to
these of control (gpA). This finding indicates that fatty mixture diet treatment is
used to evaluate the serum lipid profile parameters was able to evaluate all
parameter except HDLC measured in this trial. It was found in this study that 15%
Reducin, significantly decreases the serum TC, T.G, LDLC approximately 12%
11.% and 14% respectively (P<0.01, P<0.01 and P<0.05) of fatty mixture diet fed
rats, as shown in table.
4.4. Experimental Conditions of Clinical Trials of
Reducin:
•
AIMS AND OBJECTIVES:
By conducting these clinical trials our main objectives was, to establish the
incidence of obesity in pts presenting with high cholesterol levels & to establish
the efficacy of formulated drug in pts with obesity
4.4.1:
CONDUCTION
AND
EVALUATION
OF
CLINICAL TRIALS:
This research was conducted & evaluate & by the ethical committee of
Murshid. Hospital and health care center hub river road Karachi.
4.4.1.1: PARTICIPANTS:Hundred patients randomly selected for these trials age was (18-65) were
observed and evaluated.
4.4.1.2:DOSAGE PROTOCOL:
Reducin powdered capsules, 3 caps of 250mg were given for at least one
month (30 days). Dose regime was that one cap had to be taken in the morning
with water after breakfast, 2nd are has to be taken after lunch & third one had to be
taken at night before joining to bed.
4.4.1.3: MEASUREMENT OF MAIN OUT COME:
Main efficiency variable, T.G levels was evaluate ,pts sign & symptoms
noted which included irritability, mood alteration , insomnia, lethargy, fatigue, rest
lessens, chest heaviness was also observed. we evaluate the effects of Reducin in a
large, perspective, randomized controlled study over 30 days. The study and
analysis were planned & conducted under strict methodology.
4.4.1.4: Method:
All patients were out pts attending general clinic from the 2013 to august
2015 were divided in two gps.
The consultant gp which conducted the experiment under supervision of Dr.
Imtiaz Ahmed Channa underwent training before the study on the seek to enhance
consistency with in and b/w clinics. In each OPD clinic all assessment were made the
respective nursing staff and fill up the chart about the pts signs & symptoms. These pts
went for consultant checkup and advised cap Reducin 250mg in soft gelation cap with
pink and black color combination of zero size a/c to pharmaceutical standards. The caps
were gave tds for 30 days. The studies were perform a/c to the amount WHO guide lines
on good clinical practice.
All the pts age b/w (18-65) year were Grouped in to two divisions. Group A
includes patients containing cholesterol diet, Group B containing patients maintained on
simple diet. All the pts have obesity symptoms a/c to WHO guide lines about obesity like
increase in cholesterol, increase in wt, sweeting, lethargy, fatigue, restlessness etc.
4.4.1.5:Diagnostic Citenia for Pts:The criteria for diagnosis of problematic conditions were based on 3 main factors.
4.4.1.5.1:Types of obesity:All the pts have previous history of obesity. Types of obesity was define as by
estimating their obesity by using BMI index.
BMI = m/h2
Where m is for wt & h for height respectively.
4.4.1.5.2:Sign & Symptoms of Obesity:•
Depression
•
Disability
•
Low physical fitness
•
Negative body image
•
Negative stereotyping
•
Stigma
•
Absenteeism from work.
•
Mobility limitations
•
Reduced productivity
4.4.1.5.3: General Patients Criteria:General patient criteria established for this research in which general heath /
condition & socioeconomic status of the pts were also explained for determine the effect
of drugs on obesity.
•
Existing disease condition:-Hypertension, Diabetes, Anemia, GIT upset,
Constipation, Orthopedic Problem.
•
Daily deity pattern:
Such as low cholesterol diet and high cholesterol diet.
•
Sleep pattern: Sleep pattern and length of sleep cycle of pts were also integrated,
whether it is normal or disturbed.
•
Socio economic status: As it exerts major effects on an in dividual life, socio
economic status of pts was also kept in consideration.
4.4.1.7(a):Group A (Normal diet)
General Health (existing disease)
DISEAESES
POOR
GOOD
Normal
B.P
0%
0%
12%
Diabetes
0%
0%
08%
Anemia
0%
0%
04%
Constipation
12%
18%
15%
G.I.T Up
0%
04%
12%
Orthopedic
2%
10%
18%
Head Ache
04%
06%
10%
SET
4.4.1.7(b):Group B(Rich Fat Diet)
General Health (existing disease)
DISEAESES
POOR
GOOD
Normal
B.P
6%
10%
22%
Diabetes
04%
8%
14%
Anemia
04%
04%
04%
Constipation
12%
18%
20%
G.I.T Up
08%
14%
22%
05%
15%
25%
SET
Orthopedic
4.2: DIAGNOSIS:The diagnosis of obesity was based on two main factors, clinical and
instrumental factors, clinical and instrumental (cholesterol levels & T.G levels).
Basis of Diagnosis:
Diagnosis of obesity was made only on clinical finding in 58 of pts in
remaining 42% pts diagnosis was made on clinical findings as well as labtest as
shown on table:-
4.2.1:
•
•
Basis of diagnosis
Clinical finding
lab Test
No of cases
%
58
58%
42
42%
4.2.2: Assessment of Cholesterol level before and after the
Treatment:We evaluate the cholesterol level, BP and TGS of the pts by dividing the pt
of each gp in sub gp of ten pts.T.G.
4.2.2.1: Assesment of Cholesterol before and after treatment of
REDUCIN in Normal Diet Gp:
GPA
Sub gp
No of gps
T. G levels
{Before}
(Normal diet)
T.G Levels
{After}
I
10
155±2
140±2
II
10
159±1
146±2
III
10
156±3
139±3
IV
10
161±2
142±1
V
10
154±4
141±5
(Mean )
157
141.6
(S.D)
2.915±
2.701±
4.2.2.2: Assesment of Cholesterol before and after treatment of
REDUCIN in (Rich Fat Diet Gp):
GP B
Sub gp
No of pts
(Rich diet)
T.G Level
T.G Levels
{Before}
{After}
152+2
1
10
161+1
II
10
162±3
153±3
III
10
165±2
154±2
IV
10
167±5
152±5
V
10
169±4
156±6
Mean
166.8
155.4
S.D
3.397
3.820
4.2.3: Reduced HDLD Levels Before and After Treatment:
4.2.3.1: Reduced HDLD levels before and after treatment of REDUCIN
in Men
Gp A
(Men)
Subgp
No.of pts
before
after
1
10
40±1
38±1
II
10
42±2
37±1
III
10
45±1
39±2
IV
10
43±1
37±1
Mean
42.5
37.75
SD
2.236±
1.1169±
REDUCED HDLD:
Normal values are:
•
40mg / dl in men
4.2.3.2: Reduced HDLD Levels before and after treatment of REDUCIN in Women:
GP B
Subgp
(Women)
No. of Pts
before
after
I
10
52±2
48±1
II
10
54±1
47±2
III
10
53±2
46±1
IV
10
58±2
51±1
V
10
56±1
52±2
VI
10
55±2
48±1
(Mean)
54±66
48.66
(S.D)
2.160±
2.337±
4.2.3.2: Reduced HDLD levels before and after Treatment of REDUCIN in
Women
REDUCED HDLD:
Normal values are:
•
50 mg / dl in women
4.2.4: Reduced waist circumference before and after
Treatment:
4.2.4.1: Reduced Waist Circumference before and after Treatment of
REDUCIN in Men:
GpA
Sup gp
No of pts
before
after
Men
I
10
104cm
99cm
II
10
100cm
100cm
III
10
107cm
101cm
IV
10
107cm
101cm
V
10
108cm
102cm
Mean
106.25±
100.25±
S.D
1.707±
1.322±
4.2.4.1: Reduced Waist Circumference before and after Treatment of
REDUCIN in Men
4.2.4.2: Reduced Waist Circumference before and after
Treatment of REDUCIN in Women:
Gp B
Subgp
no of pts
before
(Women)
I
10
90cm
85cm
II
10
95cm
91cm
III
10
94cm
90cm
IV
10
96cm
91cm
V
10
98cm
92cm
VI
10
92cm
88cm
Mean
94.1
after
89.5cm
4.2.4.2: Reduced Waist Circumference before and after Treatment of REDUCIN
in Women
CHAPTER 5
5. Phytopharmaceutical Studies:5.1. Formulation of Oral dosage form of
REDUCIN:
Phytopharmaceutical studies of powder of our product Reducin was also
carried out. In this studies a 250 mg caps was prepared according to
pharmaceutical standards.
5.2. Material and Method:5.2.1. Authentication of Drug:The drug parts of individual herbs used, appox 08 kgs of all herbs was
purchased from the herbal market sadder Karachi and identified by Dr. Ghazala.H.
Rizwani (Professor, Dept of Pharmacognosy, Faculty of pharmacy, University of
Karachi). Formulation of oral dosage form of Reducin powder in such way that 4
kg was prepared in 250 mg cap capacity, soft gelatin cap were purchase from
standard drug store (shakil trader, cutchi gali No, 1 Marriott road Karachi. Many
steps were attempted for the formulation are given below:-
5.2.2. Cleansing and drying:-
The sample (herbal drugs) was quickly transferred in to a big sieve after
washing with running clear tape water, then to absorb excessive water, samples
was spread on filter paper (Whats Man No. 1) finally the sample was dried under
fan air / open air. This step has been performed on individual herbs separately.
5.2.3.Grinding:
After complete drying the drugs were grinded in to coarse powdered from
with the help of grinder (national) first individually, then after getting a coarse
powdered form of each drug, all drugs were grinded together to get fine powder of
Reducin.
5.2.4. Percolation and lyophilization:
This fine powder was percolated in 80% methanol on room temp for 15
days. The percolate was than filtered through what man filter paper No. 1. The
process was repeated for 3 times. Methanolic extract of Reducin was then
evaporated under reduced pressure and controlled temp at 400C. A brown gummy
residue was obtained which was then lyophilized and finally we obtained brown
powder of Reducin, having acrid taste, and typical herbal odour.
5.2.5. Flow ability of powder:
Powders are generally composed of solid particles of the same/ diffrent
composition having equivalent diameter, less than 1000 um along with mixing and
compaction properties, flow ability of the powder is very useful in clinical
applications of drugs when it is used in pharmaceutical dosage form. Flow ability
of powder can be checked by 2 different methods, which we used in this research.
5.2.6.Angle of repose of powder:
For the determination of cohesiveness and non-cohesiveness of the powder
of Reducin was measured by fixed cone method. For this purpose 3 gm of
powdered material was used and then the calculation of angle of repose was
measured by following equation.
Angle of repose:Tan = h/d
= tan-1 h/d
h = heigh of powder.
d = diameter of Petri dish.
S.No.
height of conical powder
Radius of petridish
1.
2.3
9.9
2.
2.5
9.9
3.
2.4
9.9
Mean
2.4
9.9
Angle of repose:
= tan-1 h/d
= tan-1 2.4/9.9
= 23.77
5.2.7. Porosity of Powder:To check the porosity of powdered drug, first a cylinder was roughly filled
up to 100 ml with powdered drug (that is called bulk volume of powder). Then the
cylinder was tapped for 100 times on smoothen surface in order to obtain the pack
volume of powder. Following observations were made during the process:-
S.
No.
Bulk vol. of
powder (ml)
Pack vol. of
powder (ml) Volume
Mean
€
%
•
100
78
•
100
77
•
100
76
77
23%
Powder porosity is another method useful in characterization of packing geometry
which linked to the bulk density of powder. The powder porosity is expressed in %
and can be calculated by two diff method. We used both methods for cross
confirmation state as under:-
Method 1 by volume:
Variable used are:Vb = bulk volume of powder
Vp = pack volume of powder
e= porosity of powder.
Formula:€ = vb – vp/vp
= 100 – 77/100 = 0.23
%€
= € x100 = 0.23 x 100 = 23%
Method 2 by density:-
Variable used are:Vb = bulk volume of powder
vp = pack volume of powder
pb = density of bulk volume
pp = density of pack powder
m = wt of powdered body.
€ = porosity of powder.
M = wt of filled (with drug) cylinder
Wt of empty cylinder
= 159.23 / 11.279
m = 46.44
Pb = m/Vp = 46.44 / 77 = 0.6031
€ – pp – pb / pp
= 0.6031 – 0.4644 / 0.6031
€ = 0.1387/0.6031 = 0.23
%€=
€ x 100
=
0.23 x 100
=
23%
Results:-
Before filling the caps we have checked the flow property of the powder
(angle of repose and porosity). The result of flow ability and porosity of Reducin
shown that the flow was up to standard limits.
5.3. Physio chemical features:
In order to determine physio chemical feature of our product Reducin below
mentioned exercises were also performed.
•
Wt variation
•
Disintegration
•
Dissolution
•
Stability
5.3.1.Wt variation:
To check the uniformity of wt of filled caps, the powdered material of
REDUCIN was filled in zero size caps (soft gelation) having pink and black color.
For the estimation of wt uniformity, wt variation was checked along with diameter
and length of caps. All caps came under the upper and lower limits of wt variation.
Cap
Cap
Cap
Cap
No.
wt length mm
length mm
Diameter mm
1
254
24.10
7.20
2
251
24.00
7.25
3
255
23.95
7.10
4
235
23.75
7.35
5
200
24.15
7.31
6
259
23.80
7.10
7
260
23.95
7.20
8
248
24.00
7.45
9.
200
24.05
7.25
10.
255
23.70
7.20
11.
250
23.85
7.25
12.
245
23.70
7.30
13.
258
23.95
7.30
14
245
24.10
7.10
15
256
24.05
7.20
16
255
23.75
7.45
17
265
23.95
7.25
18
250
24.15
7.35
19.
250
24.00
7.30
20
255
24.05
7.26
(Mean)
253.25
23.95
7.25
(S.D )
6.41
0.246
0.1060
5.3.2. Disintegration:
At least 10 caps should be used to determine the disintegration time of caps.
It was noted within a specified period when 10 caps were placed in liq medium
under the prescribed experimental condition. The minimum and maximum time
was observed b/w 8-15 mins respectively. Thus showing the disintegration time of
all 10 caps within 15 mins.
S.No
Cap
Disintegration
Mean
No
Time(min)
&
S.D
1
1
8
2
2
11
3
3
12
4
4
9
11.4
5
5
13
&
6
6
15
2.221
7
7
14
8
8
10
9
9
12
10
10
10
RESULT:
The max time for disintegration was 15min and the min time was 8 mins.
When the mean time of disintegration of 10 caps with ± S.D was is 2.221.
5.3.3. Dissolution:
Like disintegration, for dissolution we also took 10 caps for taking
observations and determine the rate at which the active drug substance dissolved in
the fluid of git. This is most suitable study (in vitro) for determining the release of
drugs.
S.No
Extent
Mean
No
of
&
Dissolution (%)
S.D
1
1
97
2
2
98
3
3
94.85
4
4
92.02
95.362
5
5
98.9
&
6
6
93.85
1.594
7
7
91
8
8
94
9
9
98
10
10
95
Results:
mins.
Cap
All the caps containing powdered drug were start dissolving in 30
CHAPTER 6
6. Result and Discussion:
In modern era, herbal medicines occupy an important and significant role for
the treatment of various diseases, although synthetic drugs and antibiotics are also
used for different diseases along with a large no of hormone balancing steroids, but
herbal medicines can be used more safely and conveniently in various regions of
the world.
Keeping all factors in mind, we have focused our research on wt reducing
herbal preparation of four plants i.e plant A: Cinnamomum cassia blume,PLANT
B:- Commiphora wightii, plant C:- Emblica officinalis plant D:- Ferula foetida
against obesity Although all best plants anciently been used for treating different
disease, especially obesity complaints and cancer complaints but they have never
been used in this combination for treating obesity.
As majority of persons suffer from obesity and its related problems we
targeted our research towards the significant effects of the herbal preparation made
from the mixed powder of all four above mentioned plants. We named this herbal
formulation Reducin.
Our research has not only been focused on the dosage formulation of
REDUCIN, but also towards the authentication, standardization and phyto
chemical investigation of compound present in these four plants (A-D). we divided
this in to four main phases given below:-
6.1. Pharmacognostic Evaluation of Plant Drugs (AD):The establishment of identification protocol or mainting is of prime
importance for herbal entity. To achieve this goal we had performed the evaluation
of plant by organoleptic, macroscopic and microscopic methods. From the former
method we got information about the sensory organs, such as external marking,
internal marking, texture, fracture color, taste, shape, size and odour of the herbal
drug while the later method revealed the presence of cellular structure and their
shape and size, if the drug is in powdered form. However the cellular arrangement
of the plant cells was determined by histological exam through microscope. In
systemic histological exam permanent slides were made of the transverse section
of the active material of the plants (A-D) used in formulation.
6.1.1. Characteristic Features of Plant A:
Pharmacognostic Featuresof Drug:
Scientific name
Cinnamomum cassia
Family
laurance
English name
Chinese cassia
Parts used
Bark, bud, flowers
Active constituents
Cinnamic
aldehyte,
Cinnamyl
acceate,
benzaldehyde, dinatal, charicol, essential oil, coumarin with constituents of
sugar fractions, crudefats and pectin, tannins and mucilage.
Action and Uses: used as flavoring agent for confectionery, deserts, pastries
and meat, old fashion pickling recipes and marinades.
Organoleptic Features:•
Texture is brittle.
•
Fracture is splintery.
•
Odour is fragment.
•
Taste is sweet, aromatic.
Microsocopic Features: stone cells, parenchymatous cells, phloem, starch
grains, caoxalate & medullay rays.
6.1.2. Characteristic Features of Plant B:Pharmacognostic Features of Drug:
Scientific name
Commiphora wigtii
Family
Burseraceae
English name
Commiphora roxburghill
Parts used
leaves, gum
Active constituent’s
essential oil, gum, resin, steroids, polymyrcene,
dimyercene, myrcene.
Action and uses: use for decrease obesity, rheumatoid arthritis, sciatica, anti
hemorrhidal, aphrodisiac agent, in menstrual problems, for treatment of cancer and
thyroid problems.
Organoleptic Features:•
Fracture is brittle.
•
Odour is bashmic.
•
Taste is bitter, acrid.
•
Texture is translucent.
•
Color is Reddish Brown.
Microscopic Features: - Spiral vessel, starch grains, stone cells, isolated
scleroids and fibers.
6.1.3. Characteristic Features of Plant C:
Pharmacognestic features of Drug:
Scientific name
Embelica officindis
Family
Euphorbiaceae
English name
Indian gooseberry
Part used
Ripe & dried fruit, seeds leafss, root, bark and flower.
Active constituent’s
Ascorbic acid, gallo tannins, mucic acid,
phyllembicacid, ellagic acid, B site sterol.
Action and uses:-used for jaundice, gonorrhea, frequent
mensturation,diabetes, poultice for skin ulcers, sores, swelling and itchness.
Organoleptic features:
•
Texture is rough.
•
Fracture is hard.
•
Color is Blackish.
•
Odour is sweet & sour.
•
Taste is sour or slightly acidic.
Microscopic Features of Drug:
Gp of phloem fibers, tannin cells, starch grain, lignified cells, ca -oxalate and
phloem vessels.
6.1.4. Characteristic Features of Plant D:Pharmacognostic Features of Drug:
Scientific name
Ferula foetida
Family
Apiaceae
English name
Lady ginia lipsky
Part used
Stems, leafs, flowers
Active constituet
Ferulic acid, umbelifarone, asaresino tannols,
fernesiferols A,B,C.
Action and use:
Antioxidant, anti-hemolytic, anticancer, control B.P, lipid
lowering agent, help to protect CNS, heart, sugar levels, it has chemotherapy
usage.
Organoleptic Features:
•
Texture is rough.
•
Fracture is hard.
•
Odour is bitter and acrid.
Powder Microscopy of Drug: Powder microscopy not done b/c it is
inorganic in nature.
6.1.5. Characteristic Features of REDUCIN:
Pharmacognostic Features of Drug:
Organoleptic features:
•
Color is brown powder.
•
Odour is fragment.
•
Taste is acrid taste.
Microscopic Features of Powder Drug: stone cells, fiber cells, caoxalate, tannin cells, starch grains and scleried.
[
Action and Uses: used successfully for true treatment of all types of obesity
as well as ovarian cysts in some obese patients.
6.2. Phytochemical Evaluation of Plant Drugs (A-D):
Then in second phase, we has performed the chromogenic testing for
knowing the existence of the naturally occurring compounds in Meoh extract of all
four plant drugs (A-D) and matched with the literature reported compounds in all
four plants. The observation was made on the basis of different coloration by
chromogenic reagent by TLC procedures for identification of different classes of
compounds such as Molish test & fehling test for carbohydrate, for protein Bioret
test, for steroids salkowski test and libermanburchad test, for alkaloids
Dragendroffs & Mayers test, for saponins froth test, for glycosides Legals test &
Lekellar killani test, for starch tannic acid test, for flavonids shinoda test, for
tannins & phenols fecl3 test, for protein Milton test & Ninhydin test and for
reducing sugar Benedicts test.
A positive responds against the specific reagent of each chemical type was
observed. Phytochemical investigations of plant drug was started from extraction,
fractionation, isolation & detection followed by chromatographic operation i.e thin
layer chromatography. In TLC the spots given by different chromogenic reagents
was noted. Like dragendroffs reagent has given orange color spots on the plate,
Cerum Amonium sulphate reagent give light green bands and light pink spots
appeared when TLC plate was observed under UV lamp.
The results obtained by phytochemical analysis of all four medicinal plants
are given below:
6.2.1 CHEMICAL COMPOSITION
carbohydrate sugar steroids protein lipid alkaloids tannin saponin
Plant A
+
+
+
+
+
+
+
+
Plant B
+
+
+
+
+
+
+
+
Plant C
+
+
+
+
+
+
+
+
Plant D
-
-
-
-
-
+
-
-
6.2.1: Chemical Composition of plant (A-D) used in the preparation of REDUCIN
6.3. Clinical Studies on REDUCIN:
It was the third and most important phase of the research studies in
which Reducin was undergone clinical trials on human subject in obesity &
its related disorders. The study was conducted and approved by the ethical
committee of Murshid hospital and health care center hub river road
Karachi. Various parameters were set for diagnostic protocol such as
Depression, low physical fitness, absenteeism from work, reduced
producing. Although all plants used in Reducin are previously used as
traditional medicine, but they have never been used before together for the
treatment of obesity. Reducin played a important and remarkable role in
this regard by producing excellent results in obese pts.
The drug given as 250 mg TDS to the patients who suffered from
obesity and its related disorders like orthopedic problem, anemia, cysts etc.
The trials was conducted on two gps A and B. group A is comprise on
simple diet gp and gp B is comprises on rich fat diet gp. Each gp had 50
participant and all had obesity & its related disorders.
Diagnosis was made by strict experimental protocol. Prior to
experimental trials we also conducted the comparative studies of pts
among gp A and B, in this study we had set the criteria for the general
health condition of participating patients by inquiring about the existing
disease [increase B.P, diabetes, anemia, GIT upset, constipation head
ache], dietary pattern (i.e simple diet, rich fat diet) and sleep pattern.
(Normal or disturbed). In this study we also kept in consideration the
socioeconomic status of participants as it exerts major effect on an
individual life. The most important analysis was that out of loo, 85 patient
belongs to poor economic class and came to patient welfare clinic (PWA) of
Murshid hospital. The symptoms which were measured are depression,
disability, low physical fitness, stigma, absent from work, reduced
productivity. After 21 days medical examination was carried out, checks
complaints, and any adverse effect and lab tests.
Assessments was made on the basis of T.G and HDLC levels of gp A
and B. the results shows a significant decrease in rich fat diet gp, T.G &
HDLC levels. Gp A also shows reduction in TGS & HDLC levels. As well as
the waist circumference which show a remarkable decrease after treatment
of Reducin in obese pts (both male & females).
6.4. Phytopharmaceutical Studies of REDUCIN:
This was the fourth phase of our research work. In this, a study of
product formulation a/c to pharmaceutical standards in oral dosage form
was carried out. During this course of study of physiochemical features of
product by wt variation, dissolution and disintegration along with stability
studies were performed. The powdered material of Reducin was filled in
zero sized caps having pink and black color combination by manual
method. Prior to filling of powder in caps, its flow property was also
checked (ie. Angle of repose and porosity) and it was found that flow was
up to standard limits.
In physiochemical features of powdered caps wt variation along with
diameter and length of caps were checked. And it was observed that the
product is of standard quality and efficacy both.
REFRENCES:
1. WHO 2000 p.6
2. Haslam DW, James WP (2005). "Obesity". Lancet (Review) 366 (9492):
1197–209. doi:10.1016/S0140-6736(05)67483-1. PMID 16198769.
3. WHO 2000 p.9
4. Kushner, Robert (2007). Treatment of the Obese Patient (Contemporary
Endocrinology). Totowa, NJ: Humana Press. p. 158. ISBN 1-59745-400-1.
Retrieved April 5, 2009.
5. Adams JP, Murphy PG (July 2000). "Obesity in anesthesia and intensive
care". Br J Anaesth 85 (1): 91–108. doi:10.1093/bja/85.1.91. PMID
10927998.
6. NICE 2006 p.10–11
7. Imaz I, Martínez-Cervell C, García-Alvarez EE, Sendra-Gutiérrez JM,
González-Enríquez J (July 2008). "Safety and effectiveness of the intragastric
balloon for obesity. A meta-analysis". Obes Surg 18 (7): 841–6.
doi:10.1007/s11695-007-9331-8. PMID 18459025.
8. Dibaise JK, Foxx-Orenstein AE (July 2013). "Role of the gastroenterologist in
managing obesity". Expert Review of Gastroenterology & Hepatology
(Review) 7 (5): 439–51. doi:10.1586/17474124.2013.811061. PMID
23899283.
9. Woodhouse R (2008). "Obesity in art: A brief overview". Front Horm Res.
Frontiers of Hormone Research 36: 271–86. doi:10.1159/000115370. ISBN
978-3-8055-8429-6. PMID 18230908.
10.Pollack, Andrew (June 18, 2013). "A.M.A. Recognizes Obesity as a Disease".
New York Times. Archived from the original on June 18, 2013.
11.Weinstock, Matthew (June 21, 2013). "The Facts About Obesity". H&HN.
American Hospital Association. Retrieved June 24, 2013.
12."Obesity". Blausen Medical. Retrieved 4 November 2015.
13.Sweeting HN (2007). "Measurement and Definitions of Obesity In Childhood
and Adolescence: A field guide for the uninitiated". Nutr J 6 (1): 32.
doi:10.1186/1475-2891-6-32. PMC 2164947. PMID 17963490.
14.NHLBI p.xiv
15.Gray DS, Fujioka K (1991). "Use of relative weight and Body Mass Index for
the determination of adiposity". J Clin Epidemiol 44 (6): 545–50.
doi:10.1016/0895-4356(91)90218-X. PMID 2037859.
16."Healthy Weight: Assessing Your Weight: BMI: About BMI for Children and
Teens". Center for disease control and prevention. Retrieved April 6, 2009.
17.Flegal KM, Ogden CL, Wei R, Kuczmarski RL, Johnson CL (June 2001).
"Prevalence of overweight in US children: comparison of US growth charts
from the Centers for Disease Control and Prevention with other reference
values for body mass index". Am. J. Clin. Nutr. 73 (6): 1086–93. PMID
11382664.
18.1 (lb/sq in) is more precisely 703.06957964 (kg/m2).
19."BMI classification". World Health Organization. Retrieved 15 February
2014.
20.Sturm R (July 2007). "Increases in morbid obesity in the USA: 2000–2005".
Public Health 121 (7): 492–6. doi:10.1016/j.puhe.2007.01.006. PMC
2864630. PMID 17399.
21.Kanazawa M, Yoshiike N, Osaka T, Numba Y, Zimmet P, Inoue S (December
2002). "Criteria and classification of obesity in Japan and Asia-Oceania".
Asia Pac J Clin Nutr. 11 Suppl 8: S732–S737. doi:10.1046/j.14406047.11.s8.19.x. PMID 12534701.
22.Bei-Fan Z (December 2002). "Predictive values of body mass index and waist
circumference for risk factors of certain related diseases in Chinese adults:
study on optimal cut-off points of body mass index and waist circumference
in Chinese adults". Asia Pac J Clin Nutr. 11 Suppl 8: S685–93.
doi:10.1046/j.1440-6047.11.s8.9.x. PMID 12534691.
23.Poulain M, Doucet M, Major GC, Drapeau V, Sériès F, Boulet LP, Tremblay A,
Maltais F (April 2006). "The effect of obesity on chronic respiratory
diseases: pathophysiology and therapeutic strategies". CMAJ 174 (9): 1293–
9. doi:10.1503/cmaj.051299. PMC 1435949. PMID 16636330.
24.Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis
RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB, Beeson WL, Clipp SL,
English DR, Folsom AR, Freedman DM, Giles G, Hakansson N, Henderson KD,
Hoffman-Bolton J, Hoppin JA, Koenig KL, Lee IM, Linet MS, Park Y, Pocobelli
G, Schatzkin A, Sesso HD, Weiderpass E, Willcox BJ, Wolk A, ZeleniuchJacquotte A, Willett WC, Thun MJ (2010). "Body-mass index and mortality
among 1.46 million white adults". The New England Journal of Medicine
363 (23): 2211–9. doi:10.1056/NEJMoa1000367. PMC 3066051. PMID
21121834.
25.Barness LA, Opitz JM, Gilbert-Barness E (December 2007). "Obesity:
genetic, molecular, and environmental aspects". American Journal of
Medical Genetics 143A (24): 3016–34. doi:10.1002/ajmg.a.32035. PMID
18000969.
26.Mokdad AH, Marks JS, Stroup DF, Gerberding JL (March 2004). "Actual
causes of death in the United States, 2000" (PDF). JAMA 291 (10): 1238–45.
doi:10.1001/jama.291.10.1238. PMID 15010446.
27.Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB (October 1999).
"Annual deaths attributable to obesity in the United States". JAMA 282 (16):
1530–8. doi:10.1001/jama.282.16.1530. PMID 10546692.
28.Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J,
Qizilbash N, Collins R, Peto R (March 2009). "Body-mass index and causespecific mortality in 900 000 adults: collaborative analyses of 57 prospective
studies". Lancet 373 (9669): 1083–96. doi:10.1016/S0140-6736(09)60318-4.
PMC 2662372. PMID 19299006.
29.Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW (October 1999).
"Body-mass index and mortality in a prospective cohort of U.S. adults". N.
Engl. J. Med. 341 (15): 1097–105. doi:10.1056/NEJM199910073411501.
PMID 10511607.
30.Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, van
der Schouw YT, Spencer E, Moons KG, Tjønneland A; et al. (November
2008). "General and abdominal adiposity and risk of death in Europe". N.
Engl. J. Med. 359 (20): 2105–20. doi:10.1056/NEJMoa0801891. PMID
19005195.
31.WHO Expert, Consultation (Jan 10, 2004). "Appropriate body-mass index for
Asian populations and its implications for policy and intervention
strategies.". Lancet 363 (9403): 157–63. doi:10.1016/s0140-6736(03)152683. PMID 14726171.
32.Manson JE, Willett WC, Stampfer MJ, Colditz GA, Hunter DJ, Hankinson SE,
Hennekens CH, Speizer FE (1995). "Body weight and mortality among
women". N. Engl. J. Med. 333 (11): 677–85.
doi:10.1056/NEJM199509143331101. PMID 7637744.
33.Tsigos C, Hainer V, Basdevant A, Finer N, Fried M, Mathus-Vliegen E, Micic
D, Maislos M, Roman G, Schutz Y, Toplak H, Zahorska-Markiewicz B (April
2008). "Management of Obesity in Adults: European Clinical Practice
Guidelines" (PDF). The European Journal of Obesity 1 (2): 106–16.
doi:10.1159/000126822. PMID 20054170.
34.Fried M, Hainer V, Basdevant A, Buchwald H, Deitel M, Finer N, Greve JW,
Horber F, Mathus-Vliegen E, Scopinaro N, Steffen R, Tsigos C, Weiner R,
Widhalm K (April 2007). "Inter-disciplinary European guidelines on surgery
of severe obesity". Int J Obes (Lond) 31 (4): 569–77.
doi:10.1038/sj.ijo.0803560. PMID 17325689.
35.Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux
L (January 2003). "Obesity in adulthood and its consequences for life
expectancy: A life-table analysis". Annals of Internal Medicine 138 (1): 24–
32. doi:10.7326/0003-4819-138-1-200301070-00008. PMID 12513041.
36.Grundy SM (2004). "Obesity, metabolic syndrome, and cardiovascular
disease". J. Clin. Endocrinol. Metab. 89 (6): 2595–600. doi:10.1210/jc.20040372. PMID 15181029.
37.Seidell 2005 p.9
38.Bray GA (2004). "Medical consequences of obesity". J. Clin. Endocrinol.
Metab. 89 (6): 2583–9. doi:10.1210/jc.2004-0535. PMID 15181027.
39.Shoelson SE, Herrero L, Naaz A (May 2007). "Obesity, inflammation, and
insulin resistance". Gastroenterology 132 (6): 2169–80.
doi:10.1053/j.gastro.2007.03.059. PMID 17498510.
40.Shoelson SE, Lee J, Goldfine AB (July 2006). "Inflammation and insulin
resistance". J. Clin. Invest. 116 (7): 1793–801. doi:10.1172/JCI29069. PMC
1483173. PMID 16823477.
41.Dentali F, Squizzato A, Ageno W (July 2009). "The metabolic syndrome as a
risk factor for venous and arterial thrombosis". Semin. Thromb. Hemost. 35
(5): 451–7. doi:10.1055/s-0029-1234140. PMID 19739035.
42.Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration
(BMI Mediated, Effects); Lu, Y; Hajifathalian, K; Ezzati, M; Woodward, M;
Rimm, EB; Danaei, G (15 March 2014). "Metabolic mediators of the effects
of body-mass index, overweight, and obesity on coronary heart disease and
stroke: a pooled analysis of 97 prospective cohorts with 1·8 million
participants.". Lancet (London, England) 383 (9921): 970–83.
doi:10.1016/S0140-6736(13)61836-X. PMID 24269108.
43.Darvall KA, Sam RC, Silverman SH, Bradbury AW, Adam DJ (February 2007).
"Obesity and thrombosis". Eur J Vasc Endovasc Surg 33 (2): 223–33.
doi:10.1016/j.ejvs.2006.10.006. PMID 17185009.
44.Yosipovitch G, DeVore A, Dawn A (June 2007). "Obesity and the skin: skin
physiology and skin manifestations of obesity". J. Am. Acad. Dermatol. 56
(6): 901–16; quiz 917–20. doi:10.1016/j.jaad.2006.12.004. PMID 17504714.
45.Hahler B (June 2006). "An overview of dermatological conditions commonly
associated with the obese patient". Ostomy Wound Manage 52 (6): 34–6,
38, 40 passim. PMID 16799182.
46.Arendas K, Qiu Q, Gruslin A (2008). "Obesity in pregnancy: pre-conceptional
to postpartum consequences". Journal of Obstetrics and Gynaecology
Canada : JOGC = Journal D'obstétrique Et Gynécologie Du Canada : JOGC 30
(6): 477–88. PMID 18611299.
47.Harney D, Patijn J (2007). "Meralgia paresthetica: diagnosis and
management strategies". Pain Med (Review) 8 (8): 669–77.
doi:10.1111/j.1526-4637.2006.00227.x. PMID 18028045.
48.Bigal ME, Lipton RB (January 2008). "Obesity and chronic daily headache".
Curr Pain Headache Rep (Review) 12 (1): 56–61. doi:10.1007/s11916-0080011-8. PMID 18417025.
49.Sharifi-Mollayousefi A, Yazdchi-Marandi M, Ayramlou H, Heidari P, Salavati
A, Zarrintan S, Sharifi-Mollayousefi A (February 2008). "Assessment of body
mass index and hand anthropometric measurements as independent risk
factors for carpal tunnel syndrome". Folia Morphol. (Warsz) 67 (1): 36–42.
PMID 18335412.
50.Beydoun MA, Beydoun HA, Wang Y (May 2008). "Obesity and central
obesity as risk factors for incident dementia and its subtypes: A systematic
review and meta-analysis". Obes Rev (Meta-analysis) 9 (3): 204–18.
doi:10.1111/j.1467-789X.2008.00473.x. PMID 18331422.
51.Wall M (March 2008). "Idiopathic intracranial hypertension (pseudotumor
cerebri)". Curr Neurol Neurosci Rep (Review) 8 (2): 87–93.
doi:10.1007/s11910-008-0015-0. PMID 18460275.
52.Munger KL, Chitnis T, Ascherio A (2009). "Body size and risk of MS in two
cohorts of US women". Neurology (Comparative Study) 73 (19): 1543–50.
doi:10.1212/WNL.0b013e3181c0d6e0. PMC 2777074. PMID 19901245.
53.Basen-Engquist, Karen; Chang, Maria (16 November 2010). "Obesity and
Cancer Risk: Recent Review and Evidence". Current Oncology Reports 13
(1): 71–76. doi:10.1007/s11912-010-0139-7. PMID 21080117.
54.Aune, D; Norat, T; Vatten, LJ (December 2014). "Body mass index and the
risk of gout: a systematic review and dose-response meta-analysis of
prospective studies.". European journal of nutrition 53 (8): 1591–601.
doi:10.1007/s00394-014-0766-0. PMID 25209031.
55.Tukker A, Visscher TL, Picavet HS (April 2008). "Overweight and health
problems of the lower extremities: osteoarthritis, pain and disability".
Public Health Nutr (Research Support) 12 (3): 1–10.
doi:10.1017/S1368980008002103. PMID 18426630.
56.Molenaar EA, Numans ME, van Ameijden EJ, Grobbee DE (November 2008).
"[Considerable comorbidity in overweight adults: results from the Utrecht
Health Project]". Ned Tijdschr Geneeskd (English abstract) (in Dutch) 152
(45): 2457–63. PMID 19051798.
57.Corona, G; Rastrelli, G; Filippi, S; Vignozzi, L; Mannucci, E; Maggi, M (2014).
"Erectile dysfunction and central obesity: an Italian perspective.". Asian
Journal of Andrology 16 (4): 581–91. doi:10.4103/1008-682X.126386. PMID
24713832.
58.Hunskaar S (2008). "A systematic review of overweight and obesity as risk
factors and targets for clinical intervention for urinary incontinence in
women". Neurourol. Urodyn. (Review) 27 (8): 749–57.
doi:10.1002/nau.20635. PMID 18951445.
59.Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyrén O (2006).
"Obesity and risk for chronic renal failure". J. Am. Soc. Nephrol. (Research
Support) 17 (6): 1695–702. doi:10.1681/ASN.2005060638. PMID 16641153.
60.Makhsida N, Shah J, Yan G, Fisch H, Shabsigh R (September 2005).
"Hypogonadism and metabolic syndrome: Implications for testosterone
therapy". J. Urol. (Review) 174 (3): 827–34.
doi:10.1097/01.ju.0000169490.78443.59. PMID 16093964.
61.Pestana IA, Greenfield JM, Walsh M, Donatucci CF, Erdmann D (October
2009). "Management of "buried" penis in adulthood: an overview". Plast.
Reconstr. Surg. (Review) 124 (4): 1186–95.
doi:10.1097/PRS.0b013e3181b5a37f. PMID 19935302.
62.Schmidt DS, Salahudeen AK (2007). "Obesity-survival paradox-still a
controversy?". Semin Dial (Review) 20 (6): 486–92. doi:10.1111/j.1525139X.2007.00349.x. PMID 17991192.
63.U.S. Preventive Services Task Force (June 2003). "Behavioral counseling in
primary care to promote a healthy diet: recommendations and rationale".
Am Fam Physician (Review) 67 (12): 2573–6. PMID 12825847.
64.Habbu A, Lakkis NM, Dokainish H (October 2006). "The obesity paradox:
Fact or fiction?". Am. J. Cardiol. (Review) 98 (7): 944–8.
doi:10.1016/j.amjcard.2006.04.039. PMID 16996880.
65.Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG,
Mookadam F, Lopez-Jimenez F (2006). "Association of bodyweight with
total mortality and with cardiovascular events in coronary artery disease: A
systematic review of cohort studies". Lancet (Review) 368 (9536): 666–78.
doi:10.1016/S0140-6736(06)69251-9. PMID 16920472.
66.Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM,
McAlister FA (July 2008). "Body mass index and mortality in heart failure: A
meta-analysis". Am. Heart J. (Meta-analysis, Review) 156 (1): 13–22.
doi:10.1016/j.ahj.2008.02.014. PMID 18585492.
67.Oreopoulos A, Padwal R, Norris CM, Mullen JC, Pretorius V, Kalantar-Zadeh
K (February 2008). "Effect of obesity on short- and long-term mortality
postcoronary revascularization: A meta-analysis". Obesity (Silver Spring)
(Meta-analysis) 16 (2): 442–50. doi:10.1038/oby.2007.36. PMID 18239657.
68.Diercks DB, Roe MT, Mulgund J, Pollack CV, Kirk JD, Gibler WB, Ohman EM,
Smith SC, Boden WE, Peterson ED (July 2006). "The obesity paradox in nonST-segment elevation acute coronary syndromes: Results from the Can
Rapid risk stratification of Unstable angina patients Suppress ADverse
outcomes with Early implementation of the American College of
Cardiology/American Heart Association Guidelines Quality Improvement
Initiative". Am Heart J (Research Support) 152 (1): 140–8.
doi:10.1016/j.ahj.2005.09.024. PMID 16824844.
69.^ Jump up to: a b c d e Lau DC, Douketis JD, Morrison KM, Hramiak IM,
Sharma AM, Ur E (April 2007). "2006 Canadian clinical practice guidelines
on the management and prevention of obesity in adults and children
summary". CMAJ (Practice Guideline, Review) 176 (8): S1–13.
doi:10.1503/cmaj.061409. PMC 1839777. PMID 17420481.
70.Bleich S, Cutler D, Murray C, Adams A (2008). "Why is the developed world
obese?". Annu Rev Public Health (Research Support) 29: 273–95.
doi:10.1146/annurev.publhealth.29.020907.090954. PMID 18173389.
71.Drewnowski A, Specter SE (January 2004). "Poverty and obesity: the role of
energy density and energy costs". Am. J. Clin. Nutr. (Review) 79 (1): 6–16.
PMID 14684391.
72.Nestle M, Jacobson MF (2000). "Halting the obesity epidemic: a public
health policy approach". Public Health Rep (Research Support) 115 (1): 12–
24. doi:10.1093/phr/115.1.12. PMC 1308552. PMID 10968581.
73.James WP (March 2008). "The fundamental drivers of the obesity
epidemic". Obes Rev (Review) 9 (Suppl 1): 6–13. doi:10.1111/j.1467789X.2007.00432.x. PMID 18307693.
74.Keith SW, Redden DT, Katzmarzyk PT, Boggiano MM, Hanlon EC, Benca RM,
Ruden D, Pietrobelli A, Barger JL, Fontaine KR, Wang C, Aronne LJ, Wright
SM, Baskin M, Dhurandhar NV, Lijoi MC, Grilo CM, DeLuca M, Westfall AO,
Allison DB (2006). "Putative contributors to the secular increase in obesity:
Exploring the roads less traveled". Int J Obes (Lond) (Review) 30 (11): 1585–
94. doi:10.1038/sj.ijo.0803326. PMID 16801930.
75."EarthTrends: Nutrition: Calorie supply per capita". World Resources
Institute. Archived from the original on 2011-06-11. Retrieved Oct 18, 2009.
76."USDA: frsept99b". United States Department of Agriculture. Retrieved
January 10, 2009.
77."Diet composition and obesity among Canadian adults". Statistics Canada.
78.National Control for Health Statistics. "Nutrition For Everyone". Centers for
Disease Control and Prevention. Retrieved 2008-07-09.
79.Marantz PR, Bird ED, Alderman MH (March 2008). "A call for higher
standards of evidence for dietary guidelines". Am J Prev Med 34 (3): 234–
40. doi:10.1016/j.amepre.2007.11.017. PMID 18312812.
80.Flegal KM, Carroll MD, Ogden CL, Johnson CL (October 2002). "Prevalence
and trends in obesity among US adults, 1999–2000". JAMA 288 (14): 1723–
1727. doi:10.1001/jama.288.14.1723. PMID 12365955.
81.Wright JD, Kennedy-Stephenson J, Wang CY, McDowell MA, Johnson CL
(February 2004). "Trends in intake of energy and macronutrients—United
States, 1971–2000". MMWR Morb Mortal Wkly Rep 53 (4): 80–2. PMID
14762332.
82.Caballero B (2007). "The global epidemic of obesity: An overview".
Epidemiol Rev 29: 1–5. doi:10.1093/epirev/mxm012. PMID 17569676.
83.Mozaffarian D, Hao T, Rimm EB, Willett WC, Hu FB (23 June 2011). "Changes
in Diet and Lifestyle and Long-Term Weight Gain in Women and Men". The
New England Journal of Medicine (Meta-analysis) 364 (25): 2392–404.
doi:10.1056/NEJMoa1014296. PMC 3151731. PMID 21696306.
84.Malik VS, Schulze MB, Hu FB (August 2006). "Intake of sugar-sweetened
beverages and weight gain: a systematic review". Am. J. Clin. Nutr. (Review)
84 (2): 274–88. PMC 3210834. PMID 16895873.
85.Olsen NJ, Heitmann BL (January 2009). "Intake of calorically sweetened
beverages and obesity". Obes Rev (Review) 10 (1): 68–75.
doi:10.1111/j.1467-789X.2008.00523.x. PMID 18764885.
86.Malik VS, Popkin BM, Bray GA, Després JP, Willett WC, Hu FB (November
2010). "Sugar-sweetened beverages and risk of metabolic syndrome and
type 2 diabetes: a meta-analysis". Diabetes Care (Meta-analysis, Review) 33
(11): 2477–83. doi:10.2337/dc10-1079. PMC 2963518. PMID 20693348.
87.Rosenheck R (November 2008). "Fast food consumption and increased
caloric intake: a systematic review of a trajectory towards weight gain and
obesity risk". Obes Rev (Review) 9 (6): 535–47. doi:10.1111/j.1467789X.2008.00477.x. PMID 18346099.
88.Lin BH, Guthrie J and Frazao E (1999). "Nutrient contribution of food away
from home". In Frazão E. Agriculture Information Bulletin No. 750:
America's Eating Habits: Changes and Consequences. Washington, DC: US
Department of Agriculture, Economic Research Service. pp. 213–239.
89.Pollan, Michael (22 April 2007). "You Are What You Grow". New York Times.
Retrieved 2007-07-30.
90.Kopelman and Caterson 2005:324.
91.Metabolism alone doesn't explain how thin people stay thin. John Schieszer
(The Medical Post).
92.Seidell 2005 p.10
93."WHO: Obesity and overweight". World Health Organization. Archived from
the original on December 18, 2008. Retrieved January 10, 2009.
94."WHO | Physical Inactivity: A Global Public Health Problem". World Health
Organization. Retrieved February 22, 2009.
95.Ness-Abramof R, Apovian CM (February 2006). "Diet modification for
treatment and prevention of obesity". Endocrine (Review) 29 (1): 5–9.
doi:10.1385/ENDO:29:1:135. PMID 16622287.
96.Salmon J, Timperio A (2007). "Prevalence, trends and environmental
influences on child and youth physical activity". Med Sport Sci (Review).
Medicine and Sport Science 50: 183–99. doi:10.1159/000101391. ISBN 9783-318-01396-2. PMID 17387258.
97.
Borodulin K, Laatikainen T, Juolevi A, Jousilahti P (June 2008). "Thirty-year
trends of
physical activity in relation to age, calendar time and birth
cohort in Finnish adults". Eur J Public Health (Research Support) 18 (3): 339–
44. doi:10.1093/eurpub/ckm092. PMID 17875578.
98.
Brownson RC, Boehmer TK, Luke DA (2005). "Declining rates of physical
activity in the United States: what are the contributors?". Annu Rev Public
Health (Review) 26: 421–43.
doi:10.1146/annurev.publhealth.26.021304.144437. PMID 15760296.
99.
Gortmaker SL, Must A, Sobol AM, Peterson K, Colditz GA, Dietz WH (April
1996). "Television viewing as a cause of increasing obesity among children in
the United States, 1986–1990". Arch Pediatr Adolesc Med (Review) 150 (4):
356–62. doi:10.1001/archpedi.1996.02170290022003. PMID 8634729.
100. Vioque J, Torres A, Quiles J (December 2000). "Time spent watching
television, sleep
duration and obesity in adults living in Valencia, Spain". Int. J.
Obes. Relat. Metab. Disord. (Research Support) 24 (12): 1683–8.
doi:10.1038/sj.ijo.0801434. PMID 11126224.
101. Tucker LA, Bagwell M (July 1991). "Television viewing and obesity in adult
females" (PDF). Am J Public Health 81 (7): 908–11. doi:10.2105/AJPH.81.7.908.
PMC 1405200.
PMID 2053671.
102. "Media + Child and Adolescent Health: A Systematic Review" (PDF). Ezekiel
J. Emanuel. Common Sense Media. 2008. Retrieved April 6, 2009.
103. Mary Jones. "Case Study: Cataplexy and SOREMPs Without Excessive
Daytime Sleepiness in Prader Willi Syndrome. Is This the Beginning of Narcolepsy
in a Five Year Old?". European Society of Sleep Technologists. Retrieved April 6,
2009.
104. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH (May
2006).
"Obesity and cardiovascular disease: pathophysiology, evaluation,
and effect of weight
968–76.
loss". Arterioscler. Thromb. Vasc. Biol. (Review) 26 (5):
doi:10.1161/01.ATV.0000216787.85457.f3. PMID 16627822.
105. Loos RJ, Bouchard C (May 2008). "FTO: the first gene contributing to
common forms of human obesity". Obes Rev (Review) 9 (3): 246–50.
doi:10.1111/j.1467-789X.2008.00481.x. PMID 18373508.
106. Yang W, Kelly T, He J (2007). "Genetic epidemiology of obesity". Epidemiol
Rev (Review)
29: 49–61. doi:10.1093/epirev/mxm004. PMID 17566051.
107. Walley AJ, Asher JE, Froguel P (June 2009). "The genetic contribution to
non-syndromic
431–42.
human obesity". Nature Reviews Genetics (Review) 10 (7):
doi:10.1038/nrg2594. PMID 19506576.
108. Farooqi S, O'Rahilly S (December 2006). "Genetics of obesity in humans".
Endocr. Rev. (Review) 27 (7): 710–18. doi:10.1210/er.2006-0040. PMID 17122358.
109. Kolata,Gina (2007). Rethinking thin: The new science of weight loss – and
the myths and realities of dieting. Picador. p. 122. ISBN 0-312-42785-9.
110. Walley, Andrew J., Asher, Julian E., Froguel, Philippe (July 2009). "The
genetic contribution to non-syndromic human obesity.". Nat Rev Genet. (Review)
10 (7): 431–42. doi:10.1038/nrg2594. PMID 19506576. However, it is also clear
that genetics greatly influences this situation, giving individuals in the same
'obesogenic' environment
significantly different risks of becoming obese.
111. Chakravarthy MV, Booth FW (2004). "Eating, exercise, and "thrifty"
genotypes: Connecting the dots toward an evolutionary understanding of
modern chronic diseases". J. Appl. Physiol. (Review) 96 (1): 3–10.
doi:10.1152/japplphysiol.00757.2003. PMID 14660491.
112. Wells JC (2009). "Thrift: A guide to thrifty genes, thrifty phenotypes and
thrifty norms". International Journal of Obesity (Review) 33 (12): 1331–1338.
doi:10.1038/ijo.2009.175. PMID 19752875.
113. Wells JC (2011). "The thrifty phenotype: An adaptation in growth or
metabolism?". American Journal of Human Biology (Review) 23 (1): 65–75.
doi:10.1002/ajhb.21100. PMID 21082685.
114. Rosén T, Bosaeus I, Tölli J, Lindstedt G, Bengtsson BA (1993). "Increased
body fat mass and decreased extracellular fluid volume in adults with growth
hormone deficiency". Clin. Endocrinol. (Oxf) 38 (1): 63–71. doi:10.1111/j.13652265.1993.tb00974.x. PMID
8435887.
115. Zametkin AJ, Zoon CK, Klein HW, Munson S (February 2004). "Psychiatric
aspects of child and adolescent obesity: a review of the past 10 years". J Am Acad
Child Adolesc Psychiatry (Review) 43 (2): 134–50. doi:10.1097/00004583200402000-00008. PMID
14726719.
116. Chiles C, van Wattum PJ (2010). "Psychiatric aspects of the obesity crisis".
Psychiatr
Times 27 (4): 47–51.
117. Yach D, Stuckler D, Brownell KD (January 2006). "Epidemiologic and
economic
consequences of the global epidemics of obesity and diabetes". Nat.
Med. 12 (1): 62–6. doi:10.1038/nm0106-62. PMID 16397571.
118. Sobal J, Stunkard AJ (March 1989). "Socioeconomic status and obesity: A
review of the
literature". Psychol Bull (Review) 105 (2): 260–75.
doi:10.1037/0033-2909.105.2.260.
PMID 2648443.
119. McLaren L (2007). "Socioeconomic status and obesity". Epidemiol Rev
(Review) 29:
29–48. doi:10.1093/epirev/mxm001. PMID 17478442.
120. Wilkinson, Richard; Pickett, Kate (2009). The Spirit Level: Why More Equal
Societies Almost Always Do Better. London: Allen Lane. pp. 91–101. ISBN 978-184614-039-6.
121. Christakis NA, Fowler JH (2007). "The Spread of Obesity in a Large Social
Network over 32 Years". New England Journal of Medicine (Research Support) 357
(4): 370–379.
doi:10.1056/NEJMsa066082. PMID 17652652.
122. Björntorp P (2001). "Do stress reactions cause abdominal obesity and
comorbidities?". Obesity Reviews 2 (2): 73–86. doi:10.1046/j.1467-
789x.2001.00027.x. PMID 12119665.
123. Goodman E, Adler NE, Daniels SR, Morrison JA, Slap GB, Dolan LM (2003).
"Impact of objective and subjective social status on obesity in a biracial cohort of
adolescents". Obesity Reviews (Research Support) 11 (8): 1018–26.
doi:10.1038/oby.2003.140. PMID 12917508.
124. Flegal KM, Troiano RP, Pamuk ER, Kuczmarski RJ, Campbell SM (November
1995). "The influence of smoking cessation on the prevalence of overweight in
the United States". N. Engl. J. Med. 333 (18): 1165–70.
doi:10.1056/NEJM199511023331801. PMID 7565970.
125. Chiolero A, Faeh D, Paccaud F, Cornuz J (1 April 2008). "Consequences of
smoking for body weight, body fat distribution, and insulin resistance". Am. J. Clin.
Nutr. (Review) 87 (4): 801–9. PMID 18400700.
126. Weng HH, Bastian LA, Taylor DH, Moser BK, Ostbye T (2004). "Number of
children associated with obesity in middle-aged women and men: results from the
health and retirement study". J Women's Health (Larchmt) (Comparative Study)
13 (1): doi:10.1089/154099904322836492. PMID 15006281.
127. Bellows-Riecken KH, Rhodes RE (February 2008). "A birth of inactivity? A
review of physical activity and parenthood". Prev Med (Review) 46 (2): 99–110.
doi:10.1016/j.ypmed.2007.08.003. PMID 17919713.
128. "Obesity and Overweight" (PDF). World Health Organization. Retrieved
February 22, 2009.
129. Caballero B (March 2001). "Introduction. Symposium: Obesity in developing
countries: biological and ecological factors". J. Nutr. (Review) 131 (3): 866S–870S.
PMID 11238776.
130. Smith E, Hay P, Campbell L, Trollor JN (2011). "A review of the association
between obesity and cognitive function across the lifespan: implications for novel
approaches to
prevention and treatment". Obesity Reviews (Review) 12 (9):
740–755. doi:10.1111/j.1467-789X.2011.00920.x. PMID 21991597.
131. DiBaise JK, Zhang H, Crowell MD, Krajmalnik-Brown R, Decker GA, Rittmann
BE (April
2008). "Gut microbiota and its possible relationship with obesity".
Mayo Clinic proceedings. Mayo Clinic (Review) 83 (4): 460–9.
doi:10.4065/83.4.460. PMID 18380992.
132. Falagas ME, Kompoti M (July 2006). "Obesity and infection". Lancet Infect
Dis (Review) 6 (7): 438–46. doi:10.1016/S1473-3099(06)70523-0. PMID 16790384.
133. Flier JS (2004). "Obesity wars: Molecular progress confronts an expanding
epidemic". Cell (Review) 116 (2): 337–50. doi:10.1016/S0092-8674(03)01081-X.
PMID 14744442.
134. Zhang, Y; Proenca, R; Maffei, M; Barone, M; Leopold, L; Friedman, JM (Dec
1, 1994). "Positional cloning of the mouse obese gene and its human
homologue.". Nature (Research Support) 372 (6505): 425–32.
doi:10.1038/372425a0. PMID 7984236.
135. Considine, RV; Considine, EL; Williams, CJ; Nyce, MR; Magosin, SA; Bauer,
TL; Rosato, EL;
Colberg, J; Caro, JF (Jun 1995). "Evidence against either a
premature stop codon or the
absence of obese gene mRNA in human obesity.".
The Journal of Clinical Investigation (Research Support) 95 (6): 2986–8.
doi:10.1172/jci118007. PMC 295988. PMID 7769141.
136. Hamann A, Matthaei S (1996). "Regulation of energy balance by leptin".
Exp. Clin.
Endocrinol. Diabetes (Review) 104 (4): 293–300. doi:10.1055/s-0029-
1211457. PMID
8886745.
137. Boulpaep, Emile L.; Boron, Walter F. (2003). Medical physiology: A cellular
and
molecular approach. Philadelphia: Saunders. p. 1227. ISBN 0-7216-3256-4.
138. Loscalzo, Joseph; Fauci, Anthony S.; Braunwald, Eugene; Dennis L. Kasper;
Hauser, Stephen L; Longo, Dan L. (2008). Harrison's principles of internal medicine.
McGraw-Hill Medical. ISBN 0-07-146633-9.
139. Satcher D (2001). The Surgeon General's Call to Action to Prevent and
Decrease
Overweight and Obesity. U.S. Dept. of Health and Human Services,
Public Health Service,
Office of Surgeon General. ISBN 978-0-16-051005-2.
140. Moyer VA (4 September 2012). "Screening for and management of obesity
in adults:
U.S. Preventive Services Task Force recommendation statement".
Annals of Internal Medicine (Practice Guideline) 157 (5): 373–8.
doi:10.7326/0003-4819-157-5-201209040-00475. PMID 22733087.
141. Brook Barnes (2007-07-18). "Limiting Ads of Junk Food to Children". New
York Times. Retrieved 2008-07-24.
142. "Fewer Sugary Drinks Key to Weight Loss - healthfinder.gov". U.S.
Department of Health and Human Services. Retrieved Oct 18, 2009.
143. Brennan Ramirez LK, Hoehner CM, Brownson RC, Cook R, Orleans CT,
Hollander M, Barker DC, Bors P, Ewing R, Killingsworth R, Petersmarck K, Schmid T,
Wilkinson W (December 2006). "Indicators of activity-friendly communities: An
evidence-based consensus process". Am J Prev Med (Research Support) 31 (6):
530–32 doi:10.1016/j.amepre.2006.07.026. PMID 17169714.
144. National Heart, Lung, and Blood Institute (1998). Clinical Guidelines on the
Identification, Evaluation, and Treatment of Overweight and Obesity in Adults
(PDF). International Medical Publishing, Inc. ISBN 1-58808-002-1.
145. Storing up problems; the medical case for a slimmer nation. London: Royal
College of Physicians. 2004-02-11. ISBN 1-86016-200-2.
146. Great Britain Parliament House of Commons Health Committee (May 2004).
Obesity –
Volume 1 – HCP 23-I, Third Report of session 2003–04. Report,
together with formal
minutes. London, UK: TSO (The Stationery Office). ISBN
978-0-215-01737-6. Retrieved 2007-12-17.
147. "Obesity: guidance on the prevention, identification, assessment and
management of
overweight and obesity in adults and children" (PDF). National
Institute for Health and Clinical Excellence(NICE). National Health Services (NHS).
2006. Retrieved April 8, 2009.
148. Wanless, Sir Derek; Appleby, John; Harrison, Anthony; Patel, Darshan
(2007). Our Future Health Secured? A review of NHS funding and performance.
London, UK: The King's
Fund. ISBN 1-85717-562-X.
149. Sacks G, Swinburn B, Lawrence M (January 2009). "Obesity Policy Action
framework and
analysis grids for a comprehensive policy approach to reducing
obesity". Obes Rev 10 (1): 76–86. doi:10.1111/j.1467-789X.2008.00524.X. PMID
18761640.
150. Strychar I (January 2006). "Diet in the management of weight loss". CMAJ
(Review) 174 (1): 56–63. doi:10.1503/cmaj.045037. PMC 1319349. PMID
16389240.
151. Shick SM, Wing RR, Klem ML, McGuire MT, Hill JO, Seagle H (April 1998).
"Persons
successful at long-term weight loss and maintenance continue to
consume a low-energy, low-fat diet". J Am Diet Assoc 98 (4): 408–13.
doi:10.1016/S0002-8223(98)00093-5. PMID 9550162.
152. Tate DF, Jeffery RW, Sherwood NE, Wing RR (1 April 2007). "Long-term
weight losses associated with prescription of higher physical activity goals. Are
higher levels of physical activity protective against weight regain?". Am. J. Clin.
Nutr. (Randomized
Controlled Trial) 85 (4): 954–9. PMID 17413092.
153. Johnston, Bradley C.; Kanters, Steve; Bandayrel, Kristofer; Wu, Ping; Naji,
Faysal;
Siemieniuk, Reed A.; Ball, Geoff D. C.; Busse, Jason W.; Thorlund,
Kristian; Guyatt, Gordon; Jansen, Jeroen P.; Mills, Edward J. (3 September 2014).
"Comparison of Weight Loss Among Named Diet Programs in Overweight and
Obese Adults". JAMA 312 (9): 923. doi:10.1001/jama.2014.10397.
154. Naude, CE; Schoonees, A; Senekal, M; Young, T; Garner, P; Volmink, J (2014).
"Low carbohydrate versus isoenergetic balanced diets for reducing weight and
cardiovascular risk: a systematic review and meta-analysis.". PLOS ONE (Research
Support) 9 (7): e100652. doi:10.1371/journal.pone.0100652. PMID 25007189.
155. Wing RR, Phelan S (2005). "Long-term weight loss maintenance". The
American Journal of Clinical Nutrition (Review) 82 (1 Suppl): 222S–225S. PMID
16002825.
156. Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T,
Tomlinson JW, Kunz R, Mol BW, Coomarasamy A, Khan KS (16 May 2012). "Effects
of interventions in pregnancy on maternal weight and obstetric outcomes: metaanalysis of randomised
evidence". BMJ (Clinical research ed.) (Meta-analysis)
344: e2088. doi:10.1136/bmj.e2088. PMC 3355191. PMID 22596383.
157. LeFevre, Michael L. (26 August 2014). "Behavioral Counseling to Promote a
Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults
With Cardiovascular Risk Factors: U.S. Preventive Services Task Force
Recommendation Statement". Annals of Internal Medicine 161: 587.
doi:10.7326/M14-1796.
158. Yanovski SZ, Yanovski JA (Jan 1, 2014). "Long-term drug treatment for
obesity: a systematic and clinical review.". JAMA: the Journal of the American
Medical Association
(Review) 311 (1): 74–86.
doi:10.1001/jama.2013.281361. PMC 3928674. PMID
24231879.
159. Rucker D, Padwal R, Li SK, Curioni C, Lau DC (2007). "Long term
pharmacotherapy for obesity and overweight: updated meta-analysis". BMJ
(Meta-analysis) 335 (7631): 1194–99. doi:10.1136/bmj.39385.413113.25. PMC
2128668. PMID 18006966.
160. Wood, Shelley. "Diet Drug Orlistat Linked to Kidney, Pancreas Injuries".
Medscape. Medscape News. Retrieved 26 April 2011.
161. Wolfe SM (21 August 2013). "When EMA and FDA decisions conflict:
differences in patients or in regulation?". BMJ (Clinical research ed.) 347: f5140.
doi:10.1136/bmj.f5140. PMID 23970394.
162. Bays HE (March 2011). "Lorcaserin: drug profile and illustrative model of the
regulatory challenges of weight-loss drug development". Expert review of
cardiovascular therapy (Review) 9 (3): 265–77. doi:10.1586/erc.10.22. PMID
21438803.
163. Bays HE, Gadde KM (December 2011). "Phentermine/topiramate for weight
reduction
and treatment of adverse metabolic consequences in obesity". Drugs
Today (Review) 47 (12): 903–14. doi:10.1358/dot.2011.47.12.1718738. PMID
22348915.
164. Colquitt, JL; Pickett, K; Loveman, E; Frampton, GK (Aug 8, 2014). "Surgery
for weight loss
in adults". The Cochrane database of systematic reviews (Meta-
analysis, Review) 8: CD003641. doi:10.1002/14651858.CD003641.pub4. PMID
25105982.
165. Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA (2014). "The
effectiveness and risks of bariatric surgery: an updated systematic review and
meta-analysis, 2003-2012". JAMA Surgery (Meta-analysis, Review) 149 (3): 275–
87. doi:10.1001/jamasurg.2013.3654. PMID 24352617.
166. Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, Lystig T,
Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A,
Jacobson P, Karlsson J, Lindroos AK, Lönroth H, Näslund I, Olbers T, Stenlöf K,
Torgerson J, Agren G, Carlsson LM
(August 2007). "Effects of bariatric surgery
on mortality in Swedish obese subjects". N. Engl. J. Med. (Research Support) 357
(8): 741–52. doi:10.1056/NEJMoa066254. PMID
17715408.
167. Weintraub, Karen. "New allies in war on weight". The Boston Globe. The
Boston Globe. Retrieved 30 June 2014.
168. "Global Prevalence of Adult Obesity" (PDF). International Obesity Taskforce.
Retrieved January 29, 2008.
169. Haslam D (March 2007). "Obesity: a medical history". Obes Rev (Review). 8
Suppl 1:31–6. doi:10.1111/j.1467-789X.2007.00314.x. PMID 17316298.
170. "Obesity and overweight". World Health Organization. Retrieved April 8,
2009.
171. Seidell 2005 p.5
172. Howard NJ, Taylor AW, Gill TK, Chittleborough CR (2008). "Severe obesity:
Investigating the socio-demographics within the extremes of body mass index".
Obesity Research & Clinical Practice 2 (1): I–II. doi:10.1016/j.orcp.2008.01.001.
PMID 24351678.
173. Tjepkema M (2005-07-06). "Measured Obesity–Adult obesity in Canada:
Measured height and weight". Nutrition: Findings from the Canadian Community
Health Survey.
Ottawa, Ontario: Statistics Canada.
174. "Online Etymology Dictionary: Obesity". Douglas Harper. Retrieved
December 31, 2008.
175. "Obesity, n". Oxford English Dictionary 2008. Retrieved March 21, 2009.
176. Zachary Bloomgarden (2003). "Prevention of Obesity and Diabetes".
Diabetes Care (Review) 26 (11): 3172–3178. doi:10.2337/diacare.26.11.3172.
PMID 14578257.
177. "History of Medicine: Sushruta – the Clinician – Teacher par Excellence"
(PDF). Dwivedi, Girish & Dwivedi, Shridhar. 2007. Retrieved 2008-09-19.
178. Theodore Mazzone; Giamila Fantuzzi (2006). Adipose Tissue And Adipokines
in Health And Disease (Nutrition and Health). Totowa, NJ: Humana Press. p. 222.
ISBN 1-58829-721-7.
179. Keller p. 49
180. Breslow L (September 1952). "Public Health Aspects of Weight Control". Am
J Public Health Nations Health 42 (9): 1116–20. doi:10.2105/AJPH.42.9.1116. PMC
1526346. PMID 12976585.
181. Puhl R, Brownell KD (December 2001). "Bias, discrimination, and obesity".
Obes. Res. (Review) 9 (12): 788–805. doi:10.1038/oby.2001.108. PMID 11743063.
182. Rubinstein S, Caballero B (2000). "Is Miss America an undernourished role
model?". JAMA (Letter) 283 (12): 1569. doi:10.1001/jama.283.12.1569. PMID
10735392.
183. Johnson F, Cooke L, Croker H, Wardle J (2008). type = Comparative Study
"Changing perceptions of weight in Great Britain: comparison of two population
surveys" Check
|url= value (help). BMJ 337: a494. doi:10.1136/bmj.a494. PMC
2500200. PMID 18617488.
184. Fumento, Michael (1997). The Fat of the Land: Our Health Crisis and How
Overweight Americans Can Help Themselves. Penguin (Non-Classics). p. 126. ISBN
0-14-026144-3.
185. Puhl R., Henderson K., and Brownell K. 2005 p.29
186. Johansson E, Böckerman P, Kiiskinen U, Heliövaara M (2009). "Obesity and
labour market success in Finland: The difference between having a high BMI and
being fat". Economics and Human Biology 7 (1): 36–45.
doi:10.1016/j.ehb.2009.01.008. PMID
19249259.
187. Cawley J, Meyerhoefer C (January 2012). "The medical care costs of obesity:
An
instrumental variables approach". Journal of Health Economics 31 (1): 219–
230. doi:10.1016/j.jhealeco.2011.10.003. PMID 22094013.
188. Finkelstein EA, Fiebelkorn IA, Wang G (1 January 2003). "National medical
spending
attributable to overweight and obesity: How much, and who's
paying". Health Affairs. Online (May). doi:10.1377/hlthaff.w3.219.
189. "Obesity and overweight: Economic consequences". Centers for Disease
Control and Prevention. 22 May 2007. Retrieved 2007-09-05.
190. Colagiuri S, Lee CM, Colagiuri R, Magliano D, Shaw JE, Zimmet PZ, Caterson
ID (2010). "The cost of overweight and obesity in Australia". The Medical Journal
of Australia (Comparative Study) 192 (5): 260–4. PMID 20201759.
191. Cummings, Laura (5 February 2003). "The diet business: Banking on failure".
BBC News. Retrieved 25 February 2009.
192. van Baal PH, Polder JJ, de Wit GA, Hoogenveen RT, Feenstra TL, Boshuizen
HC, Engelfriet
PM, Brouwer WB (February 2008). "Lifetime Medical Costs of
Obesity: Prevention No Cure for Increasing Health Expenditure". PLoS Med.
(Comparative Study) 5 (2): e29. doi:10.1371/journal.pmed.0050029. PMC
2225430. PMID 18254654.
193. Bakewell J (2007). "Bariatric furniture: Considerations for use". Int J Ther
Rehabil 14 (7): 329–33.
194. Neovius K, Johansson K, Kark M, Neovius M (January 2009). "Obesity status
and sick leave: a systematic review". Obes Rev (Review) 10 (1): 17–27.
doi:10.1111/j.1467-789X.2008.00521.x. PMID 18778315.
195. Ostbye T, Dement JM, Krause KM (2007). "Obesity and workers'
compensation: Results
from the Duke Health and Safety Surveillance System".
Arch. Intern. Med. (Research
Support) 167 (8): 766–73.
doi:10.1001/archinte.167.8.766. PMID 17452538.
196. "Alabama "Obesity Penalty" Stirs Debate". Don Fernandez. Retrieved April
5, 2009.
197. Puhl R., Henderson K., and Brownell K. 2005 p.30
198. Lisa DiCarlo (2002-10-24). "Why Airlines Can't Cut The Fat". Forbes.com.
Retrieved
2008-07-23.
199. Dannenberg AL, Burton DC, Jackson RJ (2004). "Economic and
environmental costs of
obesity: The impact on airlines". American journal of
preventive medicine (Letter) 27 (3): 264. doi:10.1016/j.amepre.2004.06.004.
PMID 15450642.
200. Lauren Cox (July 2, 2009). "Who Should Pay for Obese Health Care?". ABC
News.
201. "109th U.S. Congress (2005–2006) H.R. 554: 109th U.S. Congress (2005–
2006) H.R. 554:
Personal Responsibility in Food Consumption Act of 2005".
GovTrack.us. Retrieved 2008-07-24.
202. Basulto, Dominic (June 20, 2013). "A changing battlefield in the fight against
fat". The Washington Post. Retrieved June 20, 2013. (WebCite archive)
203. "Obesity can be deemed a disability at work - EU court". Reuters. December
18, 2014. Retrieved December 18, 2014.
204. "What is NAAFA". National Association to Advance Fat Acceptance.
Retrieved February 17, 2009.
205. "ISAA Mission Statement". International Size Acceptance Association.
Retrieved February 17, 2009.
206. Pulver, Adam (2007). An Imperfect Fit: Obesity, Public Health, and Disability
Anti-Discrimination Law. Social Science Electronic Publishing. Retrieved January
13, 2009.
207. Neumark-Sztainer D (March 1999). "The weight dilemma: a range of
philosophical perspectives". Int. J. Obes. Relat. Metab. Disord. (Review). 23 Suppl
2: S31–7. doi:10.1038/sj.ijo.0800857. PMID 10340803.
208. National Association to Advance Fat Acceptance (2008). "We come in all
sizes". NAAFA.
209. "International Size Acceptance Association – ISAA". International Size
Acceptance Association. Retrieved January 13, 2009.
210. Flynn MA, McNeil DA, Maloff B, Mutasingwa D, Wu M, Ford C, Tough SC
(February 2006). "Reducing obesity and related chronic disease risk in children
and youth: a synthesis of evidence with 'best practice' recommendations". Obes
Rev (Review). 7
Suppl 1: 7–66. doi:10.1111/j.1467-789X.2006.00242.x. PMID
16371076.
211. Dollman J, Norton K, Norton L (December 2005). "Evidence for secular
trends in
children's physical activity behaviour". Br J Sports Med (Review) 39
(12): 892–7; discussion 897. doi:10.1136/bjsm.2004.016675. PMC 1725088. PMID
16306494.
212. Metcalf B, Henley W, Wilkin T (2012). "Effectiveness of intervention on
physical activity of children: systematic review and meta-analysis of controlled
trials with objectively
measured outcomes (EarlyBird 54)". BMJ (Clinical
Research Ed.) (Review, Meta-analysis) 345: e5888. doi:10.1136/bmj.e5888. PMID
23044984.
213. Lund Elizabeth M. (2006). "Prevalence and Risk Factors for Obesity in Adult
Dogs from Private US Veterinary Practices" (PDF). Intern J Appl Res Vet Med 4
(2): 177–86.
214. McGreevy PD, Thomson PC, Pride C, Fawcett A, Grassi T, Jones B (May
2005).
"Prevalence of obesity in dogs examined by Australian veterinary
practices and the risk factors involved". Vet. Rec. 156 (22): 695–702.
doi:10.1136/vr.156.22.695. PMID
15923551.
215. Nijland ML, Stam F, Seidell JC (June 2009). "Overweight in dogs, but not in
cats, is related to overweight in their owners". Public Health Nutr 13 (1): 1–5.
doi:10.1017/S136898000999022X. PMID 19545467.
216. Bhargava A, Guthrie JF (2002). "Unhealthy eating habits, physical exercise
and macronutrient intakes are predictors of anthropometric indicators in the
Women's Health Trial: Feasibility Study in Minority Populations". British Journal of
Nutrition (Randomized Controlled Trial) 88 (6): 719–728.
doi:10.1079/BJN2002739. PMID
12493094.
217. Bhargava A (2006). "Fiber intakes and anthropometric measures are
predictors of circulating hormone, triglyceride, and cholesterol concentration in
the Women's Health Trial". Journal of Nutrition (Research Support) 136 (8): 2249–
2254. PMID 16857849.
218. Jebb S. and Wells J. Measuring body composition in adults and children
In:Peter G. Kopelman, Ian D. Caterson, Michael J. Stock, William H. Dietz (2005).
Clinical obesity in adults and children: In Adults and Children. Blackwell
Publishing. pp. 12–28. ISBN
1-4051-1672-2.
219. Kopelman P., Caterson I. An overview of obesity management In:Peter G.
Kopelman, Ian D. Caterson, Michael J. Stock, William H. Dietz (2005). Clinical
obesity in adults and
children: In Adults and Children. Blackwell Publishing.
pp. 319–326. ISBN 1-4051-1672-2.
220. National Heart, Lung, and Blood Institute (NHLBI) (1998). Clinical Guidelines
on the
Identification, Evaluation, and Treatment of Overweight and Obesity
in Adults (PDF). International Medical Publishing, Inc. ISBN 1-58808-002-1.
221. "Obesity: guidance on the prevention, identification, assessment and
management of
overweight and obesity in adults and children" (PDF). National
Institute for Health and Clinical Excellence(NICE). National Health Services (NHS).
2006. Retrieved April 8, 2009.
222. Puhl R., Henderson K., and Brownell K. Social consequences of obesity
In:Peter G. Kopelman, Ian D. Caterson, Michael J. Stock, William H. Dietz (2005).
Clinical obesity in adults and children: In Adults and Children. Blackwell
Publishing. pp. 29–45. ISBN
1-4051-1672-2.
223. Seidell JC. Epidemiology — definition and classification of obesity In:Peter
G. Kopelman, Ian D. Caterson, Michael J. Stock, William H. Dietz (2005). Clinical
obesity in adults and
children: In Adults and Children. Blackwell Publishing.
pp. 3–11. ISBN 1-4051-1672-2.
224. World Health Organization (WHO) (2000). Technical report series 894:
Obesity: Preventing and managing the global epidemic. (PDF). Geneva: World
Health Organization. ISBN 92-4-120894-5.
225. Effect of hydroxycitrate on fattyy acid synthesis by rat liver in vivo''.The
journel of biological chemistry,vol 216,no.3,issue of feb 10,pp.629-632,1971.
226. ''Safety and mechanism of appetite suppression by a novel hydroxy citric
acid extract HCA-SX '' by Ohia SE,Opere ca,Leday AM,Bgehi M,Stohs SJ, Mol QU
Biochem,2002 sep,238,89-103,PMID:12349913.
227. ''A double blinded randomized clinical study with wt level.a combination of
medicinal plants by Omair Said,Khaled Khalil,Stephen Fulder,Yousuf marie at the
open complementery medicine journel,2012,2,pp:1-6.
228. Normal caffeine consumption influence on thermogenesis and daily energy
expenditure in lean and postobase human volunteers",by AG Dullo,CA Geisser,T
Horton,A Collins,DS Miller,The American Journel of Clinical
Nutritions,USA,1989,pp:44-50.
229. HTTP://authority nutrition.com/12-weight loss pills-received/by Kris
Gunnars,bsc,dec 2015.
Raspberry ketone increases both lipolysis and fatty acid
oxidation'',by Park KS,Planta Med 2010,oct ,pp:1654-58.
230. "Identification,expression and immunoreactivity of the first coffee
allergen'', by Manavski N,Baur x,Bitner c,Int Arch Allergy
Immunol,2012,159,pp:235-42.
231. ''Dietry fiber and energy regulation",by Britt Burton-Free Man,The American
Society For Nutitional Sciences,online ISSN-1541-6100.
232. "Anti obesity mechanishm of action of conjugated linoleic acid", J Nutri
Biochem,2010 march,vol 21{3},pp:171-179.
233. "The effects of forskolin on cAMP,cGMP and free fatty acid in diet induced
obesity",by Doesyici S,Toker A,Biochem Histochem,,2014 jul,pp:388-92.
234. "Effect of p synephrine", by Stons SJ,Keith PL,Int J.M,2011 apr,pp:295-301.
235. "The Plant List".
236. Xi-wen Li, Jie Li & Henk van der Werff. "Cinnamomum cassia". Flora of
China. Missouri
Botanical Garden, St. Louis, MO & Harvard University Herbaria,
Cambridge, MA. Retrieved 28 March 2013.
237. "Cassia: A real spice or a fake cinnamon". China Business Limited as
Regency.
238. "Cassia". theepicentre.com.
239. Wong, Ming (1976). La Médecine chinoise par les plantes. Le Corps a Vivre
series. Éditions Tchou.
240. NPR: German Christmas Cookies Pose Health Danger
241. High daily intakes of cinnamon: Health risk cannot be ruled out. BfR Health
Assessment No. 044/2006, 18 August 2006 15p.
242. Yao, Ying (Mar 13, 2015). "Cinnamic aldehyde treatment alleviates chronic
unexpected stress-induced depressive-like behaviors via targeting cyclooxygenase2 in mid-aged
rats". BIOSIS 162: 97–103. doi:10.1016/j.jep.2014.12.047.
Retrieved Apr 27, 2015.
243. "Tropicos.org". Retrieved June 6, 2014.
244. "USDA GRIN Taxonomy". Retrieved 13 September 2014.
245. Sultanul Abedin And S.I. Ali. "Commiphora wightii". Flora of Pakistan 26.
246. Indian herb can reduce cholesterol, BBC NEWS, 2 May 2002
247. Murray (2012). Joseph E. Pizzorno, Jr., Michael T., ed. Textbook of natural
medicine (4th ed.). Edinburgh: Churchill Livingstone. p. 691. ISBN 9781437723335.
248. Szapary, PO; Wolfe, ML; Bloedon, LT; Cucchiara, AJ; Dermarderosian, AH;
Cirigliano, MD; Rader, DJ (2003). "Guggulipid Ineffective for Lowering Cholesterol".
JAMA 290 (6): 765–772. doi:10.1001/jama.290.6.765. PMID 12915429.
249. Sahni, S; Hepfinger, CA; Sauer, KA (2005). "Guggulipid Use in
Hyperlipidemia". Am J Health-Syst Pharm 62 (16): 1690–1692.
doi:10.2146/ajhp040580. PMID 16085931.
250. "Commiphora wightii". IUCN Red List of Threatened Species. Retrieved 12
January 2012.
251. Maheshwari, D V (8 January 2008). "Kutch to house Centre’s Rs 8-cr Guggal
conservation project". The Indian Express.
252. Paliwal, Ankur (31 July 2010). "Guggal faces sticky end". Down to Earth:
Science and Environment Online. Retrieved 12 January 2012.
253. "Education and Awareness in the 'Save Guggul Movement'". IUCN News. 31
July 2010. Retrived jan 2012.
254. "Monographs of unani medicine",vol 1,by drug control and tradational
medicinal division,National Institute of Health,ISBD,PP:411-412,485-486,514-515.
255. "Flora of west Pakistan",no 172,pp:22-23,35-36.
256. DebJC and Chandrasekhara N,"FOOD SCI"mysore 9,1960,pp:306-7.
257. Iftikhar.A.Muhammad,KBK and Muhammad,west regional labs
lahore,PAKISTAN,Pak.j.sci,1960,research 12,pp:71-73.
258. Rajeranna rao.Mr and Siddiqui HH,Indian.J.Exp.Biol,2,1964,pp:29-31.
259. Das,Phatic Chandra Brit,1976,pp:445-559.
260. Rani.G.Bala,Saroj and Grover,J.Plant Sciences,1994,pp:1-4.
261. Hu,Titanxi,Cao,Meizhen,Chen and Jiwu,Nanyuan yong fang developement
co,ltd,1994,vol 86,pp:532
262. Sagkaguchi,Noboru,Theertham.p,Jpn,Kokai,Tokkyo koho JP,2006,28,91.
263. Sharma,SK,Chandra,R,Arora,SK and Joshi,Journel of verteniary
pharmacology and toxicology,5,pp:22-25.
264. Agarwal,Ravindr kumarand Amit,Indian herbs research and pvt ltd,app
1,996 de
02,941,2005.
265. The Ayurvedic Pharmacopeia of India,vol 1,pp:43,113.
266. "Tropicos.org". Retrieved 13 September 2014.
267. Altervista Flora Italiana, genere Ferula
268. Flora of Pakistan, Ferula Linn
269. Plants for a Future, Ferula assa-foetida L., Asafoetida - Devil's Dung.
Hing
270. Graham White, National Institute of Medical Herbalists, Ferula
hermonis "The
Lebanese Viagra" by Stuart FitzSimmons
271. Nabavi SM. Ebrahimzadeh MA. Nabavi SE. Eslami B. Dehpour AA
(2011).
"Antioxidant and antihaemolytic activities of Ferula foetida regel
(Umbelliferae)". European Review for Medical & Pharmacological
Sciences 15 (2): 157–64.
272. Ackerknecht EH (1973) Therapeutics: from the Primitives to the
Twentieth Century. Hafner Press, New York.
273. AOAC (2005). Official Methods of Analysis of AOAC International,
18th edn. AOAC International, Gaithersburg, MD.
274. Barnes J, Anderson LA, Phillipson JD (2007). Herbal medicine. 3rd
Edition, Pharmaceutical Press, London. pp 1-23.
275. Bauer R (1998). Quality criteria and standardization of
phytopharmaceuticals: Can acceptable drug standards be achieved? Drug
Inform. J., 32: 101–110.
276. Bisset NG (1994). Herbal Drugs and Phytopharmaceuticals. CRC
Press, Boca Raton, FL.
277. Blumenthal M (2000) Ephedra update: industry coalition asks FDA to
adopt
national labeling guidelines on ephedra; offers co-operative
research with NIH. Herbal Gram., 50: 64-65.
278. Blumenthal M, Brusse WR, Goldberg A, Gruenwald J, Hall T, Riggins
CW, Rister RS (1998). The Complete German Commission E Monographs.
Therapeutic Guide to Herbal Medicines. The American Botanical Council,
Austin, TX.
279. Bodeker C, Bodeker G, Ong CK, Grundy CK, Burford G, Shein K
(2005). WHO
Global Atlas of Traditional, Complementary and
Alternative Medicine. World Health Organization, Geneva.
280. De Smet PAGM (2004). Health risks of herbal remedies: An update.
Clinical
Pharmacology Therapeutics, 76(1): 1–17.
281. De Smet, PAGM (1995). Health risks of herbal remedies. Drug
Safety, 13: 81-93.
282. De Smet PAGM, Keller K, Hansel R, Chandler RF (1992). Aristolochia
species In: Adverse Effects of Herbal Drugs, Springer-Verlag, Heidelberg.
1.
283. De Smet PAGM, Keller K, Hansel R, Chandler RF (1997). Adverse
Effects of Herbal Drugs, (eds), Springer-Verlag, Heidelberg. 129(3): 137145.
284. De Smet PAGM (1999). Overview of herbal quality control. Drug
Inform. J., 33: 717-724.
285. Duke JA, Martinez RV (1994). Handbook of Ethnobotanicals (Peru).
CRC Press, Boca Raton, FL.
286. EMEA (1998). Quality of Herbal Medicinal Products. Guidelines.
European Agency for the Evaluation of Medicinal Products (EMEA),
London.
287. EMEA (2002). Points to Consider on Good Agricultural and Collection
Practice for Starting Materials of Herbal Origin.
288. EMEA/HMPWP/31/99 Review. European Agency for the Evaluation of
Medicinal Products (EMEA), London.
289. EMEA (2005). Guidelines on Quality of Herbal Medicinal
Products/Traditional Medicinal Products, EMEA/CVMP/814OO Review.
European Agency for the
Evaluation of Medicinal Products (EMEA),
London.
290. Eskinazi D, Blumenthal M, Farnsworth N, Riggins CW (1999).
Botanical
Medicine: Efficacy, Quality, Assurance, and Regulation. Mary
Ann Liebert, New York.
291. Farnsworth NR, Akerele O, Bingel AS, Soejarto DD, Guo Z (1985).
World Health Organ., 63: 965.
292. Gaedcke F, Steinhoff B (2003) Quality assurance of herbal medicinal
products. In: Herbal Medicinal Products. Stuttgart: medpharm GmbH
Scientific Publishers.
pp. 37-66, 81-88.
293. Houghton P (1998). Establishing identification criteria for botanicals.
Drug Inform. J., 32: 461-469.
294. Majno GM (1975). Healing Hand: Man and Wound in the Ancient
World. Harvard University Press, Cambridge, MA.
295. Mukherjee PW (2002). Quality Control of Herbal Drugs: An Approach
to Evaluation of Botanicals. Business Horizons Publishers, New Delhi,
India.
296. Phillipson JD (1993). Quality assurance of medicinal plants. In: Franz
C et al.
First World Congress on medicinal and aromatic plants for
human welfare, WOCMAP, quality, phytochemistry, industrial aspects,
economic aspects. Acta
Horticult., 333: 117-122.
297. Roberts JE, Tyler VE (1997). Tyler’s Herbs of Choice. The
Therapeutic Use of Phytomedicinals. The Haworth Press, New York.
298. Solecki RS (1975). Standardized product as well as the quality of the
consumer information on the herbal remedy. hanidar IV. Science, 190:
880.
299.2 Int. J. Biodvers. Conserv.
300. (2007). Herbal medicine and its standardization. Pharma. info., 1: 6.
301.Watson DG (1999). Pharmaceutical Analysis. Churchill Livingstone,
Edinburgh.
302.WHO (1979). The International Pharmacopeia, General Methods of
Analysis, 3rd
edn. World Health Organization, Geneva. 1.
303.WHO (1988a). The International Pharmacopeia,Quality Specifications
for Pharmaceutical Substances, Excipients, and Dosage Forms, 3rd edn.
World
Health Organization, Geneva. 3.
304.WHO (1988b). Quality Control Methods for Medicinal Plant Materials.
World
Health Organization, Geneva.
305 WHO (1990). The Use of Essential Drugs. Eighth report of the WHO
Expert committee. World Health Organization, Geneva.
306 WHO (1992). Quality Control Methods for Medicinal Plant Materials.
World
307 WHO (1996a). Quality Assurance of Pharmaceuticals: A Compendum
of
Guidelines and Related Materials, Good Manufacturing Practices and
Inspection. World Health Organization, Geneva. 2.
308 WHO (1996b). Guidelines for the Assessment of Herbal Medicines.
WHO Technical Report Series, World Health Organization, Geneva. 863.
309.WHO (1998a). Quality Control Methods for Medicinal Plant Materials,
World
310. WHO (1998b). Guidelines for the Appropriate Use of Herbal
Medicines. WHO Regional Publications, Western Pacific Series. WHO
Regional office for the Western Pacific, Manila. 3.
311. WHO (1998c). Basic Tests for Drugs, Pharmaceutical Substances,
Medicinal Plant Materials and Dosage Forms. World Health Organization,
Geneva.
312. WHO (1999a). Quality Control Methods for Medicinal Plant Materials.
World
313. WHO (1999b). WHO Monographs on Selected Medicinal Plants,
World Health Organization, Geneva. 1.
314. WHO (2000). General Guidelines for Methodologies on Research and
Evaluation of Traditional Medicine. World Health Organization, Geneva
.
315. WHO (2000). The WHO Recommended Classification of Pesticides
by Hazard and Guidelines to Classification 2000–2002 (WHO/PCS/01.5).
International
Programme on Chemical Safety, World Health
Organization, Geneva.
316. WHO (2002a). WHO Monographs on Selected Medicinal Plants,
World Health Organization, Geneva. 2.
317. WHO (2002b). Ancient Remedies, New Disease. World Health
Organization, Geneva.
318. WHO (2002c). General Guidelines for Methodologies on Research
and Evaluation of Traditional Medicine. World Health Organization,
Geneva.
319. WHO (2003). WHO Guidelines on Good Agricultural and Collection
Practices
(GACP). World Health Organization, Geneva.
320. WHO (2004). Guidelines on Good Agricultural and Collection
Practices (GACP) for Medicinal Plants. World Health Organization,
Geneva.
321. WHO (2005). WHO Global Atlas of Traditional, Complementary and
Alternative Medicine. World Health Organization, Geneva. 1and 2.
322. U.S. Preventive Services Task Force. Screening for an dmanagement of
obesity in adults. Ann Intern Med. 2012;157(5):373-378.
323. . American Academy of Family Physicians. Obesity in adults (screening for
and management). www.aafp.org/online/en/home/clinical/exam/obesity.html.
Accessed Jan. 20, 2013.
324. Kraschnewski JL, Sciamanna CN, Stuckey HL, et al. Asilent response to the
obesity epidemic: Decline in U.S. physicianweight counseling. Med Care.
2013;51(2):186-192.
325. Clinical guidelines on the identification, evaluation, and treatment of
overweight and
obesity in adults: The evidence
330. report. Bethesda, Md.: National Heart, Lung and BloodInstitute, 1998; NIH
98-4083.
326. Smith AW, Borowski LA, Liu B, et al. U.S. primary carephysicians’ diet-,
physical activity-, and weight-related careof adult patients. Am J Prev Med.
2011;41(1):33-42.
327. Potter MB, Vu JD, Croughan-Minihane M. Weight management:What
patients want from their primary care physicians.J Fam Pract. 2001;50(6):513518
328. Sesselberg TS, Klein JD, O’Connor KG, et al. Screening and counseling for
childhood
obesity: Results from a nationalsurvey. J Am Board Fam Med.
2010;23(3):334-342
.
.
329. . Bleich SN, Bennett WL, Gudzune KA, et al. Impact of physician BMI on
obesity care and beliefs. Obesity (SilverSpring). 2012;20(5):999-1005.
330. Post RE, Mainous AG 3rd, Gregorie SH, et al. The influence of physician
acknowledgment of patients’ weight statuson patient perceptions of
overweight and obesity in the United States. Arch Intern Med.2011;171(4):316321.
331. Gaglioti A, Petterson SM, Bazemore AW, et al. Primarycare’s ecologic
impact on obesity. Am Fam Physician. 2009;79(6):446.
.
332. . Centers for Disease Control and Prevention. Obesity andoverweight for
professionals:
Adult obesity facts. www.cdcgov/obesity/data/adult.html.
Accessed Jan. 22, 2013
professionals:
Childhood data. www.cdc.gov/obesity/data/childhood.html.
Accessed Jan. 22, 2013.
334. Pan L, Blanck HM, Sherry B, et al. Trends in the prevalence of extreme
obesity among U.S. preschool-agedchildren living in low-income families, 19982010. JAMA.2012308(24):2563-2565
professionals:
Adult causes. www.cdc.gov/obesity/adult/causes/index.html.
Accessed Jan. 22, 2013
336. Karasu SR. Of mind and matter: Psychological dimensionsin obesity. Am J
Psychother. 2012;66(2):111-128.
337. . Goacher PJ, Lambert R, Moffatt PG. Can weight-relatedhealth risk be more
accurately assessed by BMI, or by genderSpecific calculations of percentage body
fatness? MedHypotheses. 2012;79(5):656-662.
338. Romero-Corral A, Somers VK, Sierra-Johnson J, et al.Accuracy of body
mass index in
diagnosing obesity in theadult general population. Int J Obes
(Lond). 2008;32(6):
356. 959-966.
339. Institute for Clinical Systems Improvement. Preventionand management of
obesity (mature adolescents andadults). Bloomington, Minn.: Institute for Clinical
SystemsImprovement, 2011
340. Ghandehari H, Le V, Kamal-Bahl S, et al. Abdominalobesity and the
spectrum of global
cardiometabolic risks inU.S. adults. Int J Obes (Lond).
2009;33(2):239-248.
341. . Dunkley AJ, et al. Waist circumference measurement:Knowledge, attitudes
and barriers in patients and practitionersin a multi-ethnic population. Fam Pract.
2009;26(5):365-371
342. . Bray GA. Screening for and clinical evaluation of obesity
inadults.www.UpToDate.com. Accessed Jan. 30, 2013.
343. Centers for Disease Control and Prevention. Healthyweight: Assessing your
weight www.cdc.gov/healthyweight/assessing/index.html. Accessed Feb. 3, 2013.
344. Bosy-Westphal A, Booke CA, Blocker T, et al. Measurementsite for waist
circumference
affects its accuracy as anindex of visceral and abdominal
subcutaneous fat in a Caucasianpopulation. J Nutr.
2010;140(5):954-961.
345. . E rvin RB. Prevalence of metabolic syndrome among adults20 years of age
and over, by sex, age, race and ethnicity, andbody mass index: United States,
2003–2006. Natl HealthStat Report. 2009 May
5;(13):1-7.
346. . Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis andmanagement of
the metabolic
syndrome: An American Heart Association/National Heart,
Lung, and Blood Institute scientificstatement. Circulation.
2005;112(17):2735-2752.
347. Armstrong C. AHA and NHLBI review diagnosis andmanagement of the
metabolic
syndrome. Am Fam Physician.2006;74(6):1039-1047.
348. Kolasa KM, Collier DN, Cable K. Weight loss strategiesthat really work. J
Fam Pract. 2010;59(7):378-385.
349. . Diabetes Prevention Program (DPP). National DiabetesInformation
Clearinghouse.
diabetes.niddk.nih.gov/dm/pubs/preventionprogram. Accessed
Feb. 12, 2013.
350. . Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction metformin. N
Engl J Med. in the incidence of type 2 diabetes with lifestyle
interventionor2002;346(6):393-403.
351. . Bray GA. Behavioral strategies in the treatment of
obesity.www.UpToDate.com. Accessed Jan. 15, 2013.
352. LeBlanc ES, O’Connor E, Whitlock EP,et al. Effectivenessof primary carerelevant
treatments for obesity in adults: ATask Force. Ann Intern Med.
2011;15(7)5:434-447.
353. Rao G. Office-based strategies for the management of obesity.Am Fam
Physician. 2010;81(12):1449-1456.
354. Poston WS, Foreyt JP. Successful management of the obesepatient. Am Fam
Physician. 2000;61(12):3615-3622.
355. . Searight HR. Realistic approaches to counseling in theoffice setting. Am
Fam Physician.
2009;79(4):277-284.
356. Pollak KI, Alexander SC, Tulsky JA, et al. Physician empathyand listening:
Associations with patient satisfaction and autonomy. J Am Board Fam Med.
2011;24(6):665-672.
357. Teixeira PJ, et al. Motivation, self-determination, and longtermweight
control. Int J
358.
Behav Nutr Phys Act. 2012 Mar 2;9:22
Shick SM, Wing RR, Klem ML, et al. Persons successfulat long-term
weight loss and
maintenance continue toconsume a low-calorie, low-fat diet. J
Am Diet Assoc. 1998;98(4):408-413
359. Klem ML, Wing RR, McGuire MT, et al. A descriptivestudy of individuals
successful at long-term maintenance ofsubstantial weight loss. Am J Clin Nutr.
1997;66(2):239-246.
360. Wadden TA, Volger S, Sarwer DB, et al. A two-year randomizedtrial of
obesity treatment in primary care practice.N Engl J Med. 2011;365(21):1969-1979.
361. Department of Health and Human Services. DietaryGuidelines for
Americans 2010. www.cnpp.usda.gov/DGAs2010-PolicyDocument.htm.
Accessed Feb. 13, 2013.
362.
Casazza K, Fonatine KR, Astrup A, et al. Myths, presumptions,and facts
about obesity.
N Engl J Med. 2013;368(5): 446-454.
.
363. Heymsfield SB, van Mierlo CA, van der Knaap HC, et al.Weight
management using a
meal replacement strategy:
meta and pooling
analysis from six studies. Int J Obes RelatMetab Disord. 2003;27(5):537-549.
364. Haas WC, Moore JB, Kaplan M, et al. Outcomes from amedical weight loss
program: Primary care clinics versusweight loss clinics. Am J Med.
2012;125(6):603-611.
365. Sacks FM, Bray GA, Carey VJ, et al. Comparison ofweight-loss diets with
different compositions of fat, protein, and carbohydrates. N Engl J Med.
2009;360(9):859-873.
366. Hall KD, Sacks G, Chandramohan D, et al. Quantificationof the effect of
energy
imbalance on bodyweight. Lancet. 2011;378(9793):826-837.
367. Franz MJ, VanWormer JJ, Crain AL, et al. Weight-loss outcomes:A
systematic review and meta-analysis of weight-loss(10):175clinical trials with a
minimum 1-year follow-up. J Am DietAssoc.
2007;1075-1767.
368. Bray GA. Dietary therapy for obesity www.UpToDate.com.eAccessd Jan.
15, 2013.
369. Leibel RL, Rosenbaum M, Hirsch J, et al. Changes inenergy expenditure
resulting from altered body weight.N Engl J Med. 1995;332(10):621-628.
370. Hemmingsson E, Johansson K, Eriksson J, et al. Weightloss and dropout
during a
commercial weight-loss program including a very-low-calorie diet, a
low-calorie diet,
orrestricted normal food: Observational cohort study. AmJ Clin
Nutr. 2012;96(5):953-961.
371. . Heshka S, Anderson JW, Atkinson RL, et al. Weight losswith self-help
compared with a
structured commercial program: A randomized trial. JAMA.
2003;289(14):1792-1798.
372. . Rock CL, Flatt SW, Sherwood NE, et al. Effect of a freeprepared meal and
incentivized weight loss program onweight loss and weight loss maintenance in
obese andoverweight women: A randomized
controlled trial. JAMA.
2010;304(16):1803-1810.
373. Tsai AG, Wadden TA. Systematic review: An evaluationof major
commercial weight loss programs in the United States. Ann Intern Med.
2005;142(1):56-66.
374. . Department of Health and Human Services. 2008 PhysicalActivity
Guidelines for Americans.
www.health.gov/PAGUIDELINES/guidelines/default.aspx. Accessed Feb.13,
2013.
375. . Bray GA. Role of physical activity and exercise in
obesity.www.UpToDate.com. Accessed Feb. 13, 2013.
376. Coleman KJ, Ngor E, Reynolds K, et al. Initial validationof an exercise
‘vital sign’ in
electronic medical records. Med Sci Sports Exerc.
2012;44(11):2071-2076.
377. Laskowski ER. The role of exercise in the treatment of obesity.of an exercise
‘vital sign’ in electronic medical records. MedPM R. 2012;4(11):840-844.
378. Ferrari CKB. Metabolic syndrome and obesity: Epidemiologyand prevention
by physical activity and exercise. J Exer Sci Fit. 2008;6(2):87-96.
379. National Institute of Diabetes and Digestive and KidneyDiseases.
Prescription medications for the treatment of obesity.
win.niddk.nih.gov/publications/prescription.htm#meds. Accessed July 18,
2012.
380. . Bray GA. Drug therapy of obesity. www.UpToDate.com.Accessed Jan. 15,
2013.
381. Taylor JR, Dietrich E, Powell JG. New and emerging
pharmacologictherapies for type 2
diabetes, dyslipidemia, and obesity. Clin
Ther. 2013;35:A3-17.
382. Carter R, Mouralidarane A, Ray S, et al. Recent advancementsin drug
treatment of obesity. Clin Med. 2012; 12(5):456-460.
383. Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapiesfor obesity:
Past, current, and future therapies. J Obes. 2011;2011:179674. Epub 2010 Dec 12.
384. Wilbert B, Mohundro BL, Shaw V, et al. Appetite suppressantsas adjuncts
for weight loss. Am Fam Physician. 2011; 83(7):1-2.
385. Orlistat (Xenical) prescribing information. San Francisco,Calif.: Genentech,
Inc., 2012.
386. E pocrates Online. www.Epocrates.com. Accessed Feb. 25,2013.
387. Lorcaserin (Belviq) prescribing information. WoodcliffLake, N.J.: Arena
Pharmaceuticals, 2012.
388. U.S. Food and Drug Administration. Consumer updates:Medication target
long-term weight control.
www.fda.gov/ForConsumers/ConsumerUpdates/ucm312380.htm.Accessed Feb.
13, 2013
.
389. Arena Pharmaceuticals provides corporate updateand reviews fourth quarter
and full year
2012 financial results.
invest.arenapharm.com/releasedetail.cfm?ReleaseID=744786. Accessed March 7,
2013.
390. Federal Register. Schedules of Controlled Substances:Placement of
Lorcaserin into Schedule IV. federalregister. gov/a/2012-30531. Accessed March 7,
2013.
391. Phentermine and topiramate extended-release (Qsymia)prescribing
information.Mountain View, Calif.: Vivus, Inc., 2012..
392. U.S. Food and Drug Administration. FDA approvesweightmanagementQsymiwww.fda.gov/NewsEvents/Newsroom/PressAnnouncements/uc
m312468.htm.Accessed Feb. 14, 2013.
393. Andrews RA, Lim RB. Surgical management of severe obesity.Accessed
Feb. 13, 2013.
394. Sjostrom L, Narbro K, Sjostrom D, et al. Effects of bariatricsurgery on
mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-752.
395. Adams TD, Gress RE, Smith SC, et al. Long-term mortalityafter gastric
bypass surgery.
N Engl J Med. 2007;357(8): 753-761.
396. . SAGES Guidelines Committee. SAGES guideline for clinicalapplication of
laparoscopic bariatric surgery. Surg Obes Relat Dis. 2009;5(3):387-405.
397. . DeMaria EJ. Bariatric surgery for morbid obesity. N Engl JMed.
2007;356(21):2176-2183.
398. O’Brien PE, MacDonald L, Anderson M, et al. Long-termoutcomes after
bariatric
surgery: Fifteen-year follow-up ofadjustable gastric banding and a
systematic review of thebariatric surgical literature. Ann Surg. 2013;257(1):87-94.
399. Vest AR, Heneghan HM, Aqarwal S, et al. Bariatric surgeryand
cardiovascular outcomes: A systematic review. Heart. 2012;98(24):1763-1777.
400. Buchwald H, Estok R, Fahrbach K, et al. Weight and type2 diabetes after
bariatric
surgery: Systematic review and meta-analysis. Am J Med.
2009;122(3):248-256.
401. Sjostrom L. Review of the key results from the SwedishObese Subjects
(SOS) trial: A
prospective controlled intervention study of bariatric surgery. J
Intern Med. 2013;273(3):219-234.
402. . Colquitt JL, Picot J, Loveman E, et al. Surgery for obesity.Cochrane
Database Syst Rev.
2009;2:CD003641.
.
403. Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastricbanding and
conventional
therapy for type 2 diabetes: A randomized controlled trial.
JAMA. 2008;299(3):316-323.
404. Flum DR, Belle SH, King WC, et al. Perioperative safety inthe longitudinal
assessment of bariatric surgery. N Engl J Med. 2009;361(5):445-454.
405. . de Zwaan M, Hilbert A, Swan-Kremeier, et al. Comprehensiveinterview
assessment of
eating behavior 18-35 months after gastric bypass surgery for
morbid obesity. Surg
ObesRelat Dis. 2010;6(1):79-85.
406. Sarwer DB, Dilks RJ, West-Smith L. Dietary intake andeating behavior after
bariatric
surgery: Threats to weight loss maintenance and strategies for success.
Surg Obes RelatDis. 2011;7(5):644-651.
407. U.S. Preventive Services Task Force. Screening for obesityin children and
adolescents: Recommendation statement Am Fam Physician. 2011;83(6):739-740.
408. Waters E, de Silva-Sanigorski A, Hall BJ, et al. Interventionsfor preventing
obesity in
children. Cochrane Database Syst Rev. 2011;12:CD001871.
409. Centers for Disease Control and Prevention. Basics aboutchildhood obesity
www.cdc.gov/obesity/childhood/basics.html. Accessed Feb. 15, 2013.
410. American Academy of Pediatrics. Prevention of pediatricoverweight and
obesity. Pediatrics. 2003;112(2):424-430.
411. American Academy of Pediatrics. Healthy Active LivingFor Families
(HALF). www2.aap.org/obesity/HALF.html. Accessed Feb. 14, 2013.
412. American Academy of Pediatrics. Media use by childrenyounger than 2
years. Pediatrics.2011;128(5);1040-1045.
413. American Academy of Family Physicians joins First LadyObama’s effort to
end
childhood obesity. www.aafp.org/
online/en/home/media/releases/2010b/lets-movchilhoodobesity.html. Accessed
Feb.14,2013.
414. Bambs C, Reis SE. Embracing primordial prevention forideal cardiovascular
health.
Future Cardiol. 2011;7(4):447-450.
415. . Weintraub WS, Daniels SR, Burke LE, et al. Value of primordialand
primary prevention
for cardiovascular disease: and primary prevention for
cardiovascular disease:A policy
statement from the American Heart
Association.Circulation. 2011;124(8):967-990.
416. . Institute of Medicine. Accelerating progress in obesity prevention:Solving
the weight of
the nation. Washington, D.C.: National Academies Press,
2012.24 Diagnosis and
Management of Obesity
417.Miller Keone Encyclopedia and Dictionary of Medicine,7th Edition 2003 by
Saunders.
418.Mobsby Medical Dictionay, 9TH Edition 2009@Elsevier.
419.Herbs for Obesity@Histolic online.com, wt control info center 2013 ICBS.Inc.
420.AMDA The Society for Post-Acute and Long-Term Care Medicine (February
2014), "Ten Things Physicians and Patients Should Question", Choosing Wisely: an
initiative of the ABIM Foundation (AMDA – The Society for Post-Acute and LongTerm Care Medicine), retrieved 20 April 2015.
421.Pollack, Andrew (29 January 2013) F.D.A. Approves Genetic Drug to Treat
Rare Disease The New York Times, Retrieved 31 January 2013.
422.Staff (29 January 2013) FDA approves new orphan drug Kynamro to treat
inherited cholesterol disorder U.S. Food and Drug Administration, Retrieved 31
January 2013.
423. Koren MJ, Scott R, Kim JB et al Lancet 2012; 380:1995-2006.
424.Gugliano RP, Desai NR, Kohli P et al Lancet 2012; 380:2007-17.
425.Antonio M Gotto,jr,MD Mphil,Omega 3 and Other Novel Pharmacological
Approches in Management of Hyperlipidemia@Multidisciplinary 1994-2016.

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