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ParActin : Scientific
Breakthroughs for Bone,
Joint and Muscle Health
®
An eBook brought to you by
Informing and Educating Natural Products Retailers On Dietary Supplements, Herbs, HABA, Homeopathy, Foods
Sponsored by
Supplier of
Table of Contents
3 Fighting Inflammation, The Body’s Silent Killer
4 NF-kB: The Master Inflammation Switch
4 ParActin : The Natural NF-kB
®
Inhibitor
5 Keep Moving! Joint, Bone &
Muscle Health for Everybody
5 ParActin : Healthy Joint Support
8 ParActin : Healthy Bone Support
10 ParActin : Healthy Cartilage Support
12 ParActin : Muscle Health and Recovery
16 ParActin : Masters the Immune Balancing Act
17 ParActin : Organic, Non-GMO, Vegan Choice
18 FAQs
19 References
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Fighting Inflammation, The Body’s Silent Killer
What’s scarier than the boogeyman you know? The boogeyman you don’t
know. Well, chronic inflammation is indeed the boogeyman you don’t know
because it isn’t felt until the pain or dysfunction from years of its silent reign
inspire physician visits.
Cancer. Alzheimer’s. Autoimmune diseases. Depression. What do all these
conditions have in common? They have been linked to chronic inflammation.
It seems impossible that one thing can be responsible for so many problems,
but a growing body of medical research is revealing that long-term, systemic
inflammation that occurs when one’s immune system goes into overdrive—
sending out cells that attack healthy tissues, along with the unhealthy—may be
at the root of many prevalent diseases.
The medical and nutraceutical research communities are highly aware how
chronic inflammation damages the human organism in many ways. In vivo
research has outlined and clarified the cascade of reactions causing unhealthy
inflammation.
Figure 1: Inflammatory Response
Inflammation, however, is not an unjustified biological response. It is critical for our
survival and is the body’s natural mechanism to defend against a diverse variety of
pathogens including bacteria, viruses, fungi,
tumors and other harmful agents (e.g., chemWhen cells are injured, the mast cells
icals, radiation, burns and wounds). Inflamsignal an inflammatory response through
a series of biochemical signals. NF-kB is
mation is a complex reaction of the body in
released and results in the expression
of several pro-inflammatory proteins
(e.g. COX2 and iNOS) and proresponse to cellular injury (such as a bruise).
inflammatory cytokines (e.g.
interleukin-2, interferon-gamma)
It is marked by tissue swelling, capillary dilation, antihistamine activity, redness, heat and
pain. It serves as a mechanism initiating the elimination of noxious agents and
of damaged tissue (see Figure 1).
3
Two types of inflammation are associated with imbalanced immunity.
Classical inflammation is usually associated with pain and may result from
an overactive immune system that is constantly “turned on.” This causes the
self-attack mode that can lead to several disorders such as irritable bowel
syndrome, psoriasis and rheumatoid arthritis, among others. Silent inflammation happens when the immune system continues its self-attack mode at the
cellular level, affecting certain organs such as the heart or brain without the
individual perceiving pain or discomfort. He or she may experience fatigue,
muscle stiffness and headaches, however.
As we age, our immune systems go
downhill, providing us with an ever-smaller
reservoir of cells capable of responding to
the increasing amount of damage inside
the body and tissues. It’s a sad story. The
body hurts itself by trying to fix problems it
can’t resolve.
Most people reach for common nonsteroidal anti-inflammatory drugs (NSAIDs)
like aspirin and ibuprofen to ease aches
and pains when we bang up muscles
or joints or experience headaches and
colds. Unfortunately, NSAIDs can rip the
stomach lining and gastrointestinal tract,
contributing to even more inflammation in
the long run. COX-2-inhibitor drugs were
designed to block just the inflammatory functions of the COX-2 enzyme, leaving the stomach-protecting functions of COX-1 intact. However, research has
shown an increased risk of heart attack and stroke among users.
The current hot theory suggests that depression may be caused by cytokine-driven inflammation in the brain. A study published in JAMA Psychiatry
found that people with clinical depression had levels of brain inflammation
30% higher than those in a control group (1). This may be one reason why half
of clinically depressed people don’t respond to antidepressants; they cannot
tackle inflammation levels.
4
NF-kB: The Master Inflammation Switch
Implicated in the onset of 95% of all cancers is a common but under-recognized molecule most people have never heard of: nuclear factor-kappaB (NFkB). Emerging research validates the danger it poses to maturing individuals.
NF-kB is a protein that acts as a switch to turn inflammation on and off in
the body. Scientists describe NF-kB as a “smoke sensor” that detects dangerous threats like free radicals and infectious agents. In response to these
threats, NF-kB “turns on” genes that produce inflammation. As we age, NF-kB
expression in the body increases, provoking widespread chronic inflammation
and setting the stage for diseases ranging from atherosclerosis and diabetes
to Alzheimer’s. Evidence from recent research suggests that by inhibiting
NF-kB, a wide range of diseases and conditions in which inflammation plays a
critical role can be treated (see Figure 2).
Central nervous system:
Neurodegeneration
Lung:
Neutrophilic alveolitis
Asthma
Liver:
Hepatitis
Cardiovascular system:
Ischemia/reperfusion
Septic Shock
Gastrointestinal tract:
Inflammatory bowel
disease
Kidney:
Glomerulonephritis
Articular joint:
Rheumatoid arthritis
Figure 2: Inflammatory Diseases
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ParActin®: The Natural NF-kB Inhibitor
ParActin® helps balance and calm over-protective immune cells. Andrographolides in ParActin® can exert their beneficial effects through PPAR gamma
activation (i.e., PPAR gamma agonist), which effectively turns off the “master
power switch” NF-kB, responsible for exerting the over-reactive inflammatory
response. By deactivating NF-kB, the hyperexpression of cytokines, proinflammatory proteins and enzymes such as COX-2, PGE2, interleukin-2 and
interferon gamma is reduced (see Figure 3).
ParActin® is a patented extract from the plant called Andrographis paniculata, standardized to andrographolide, 14 deoxyandrographolide and neoandrographolide. These naturally occurring phytochemicals in the Andrographis
paniculata plant have been shown by researchers to have beneficial actions
in supporting healthy joints, bones and muscles; this is so important in today’s
active lifestyle. ParActin® was awarded U.S. Patent #8,084,495 B2 (Dec. 27,
2011), titled, “Composition of Labdane Diterpenes Extracted from Andrographis paniculata, Useful for the Treatment of Autoimmune Diseases, and Alzheimer’s Disease by Activation for PPAR-Gamma Receptors.”
Figure 3: PPAR gamma Activation
PPARγ activated
NFκB inhibited
Inflammatory
Cytokines reduced
(TNFα, IL-6,
IL-1β, IL-2)
T Cell deactivation
Inflammatory Proteins
Deactivated
Stat 1
COX2
iNOS
IFNγ
prostaglandins
6
NO2
Andrographis has a long and rich history of use in Asia where it is called
the “King of Bitters.” In the venerable medicinal systems of Ayurveda and
traditional Chinese medicine, practitioners provide or recommend this herb for
many maladies and for adaptogenic (i.e., to help the body adapt, balance) support. Interestingly, its traditional uses are what modern medicine now knows as
the source of unhealthy inflammatory response.
ParActin® is the result of 20 arduous years of research and development.
It boasts more than 30 studies, including in vitro, in vivo animal models and
human clinical trials. ParActin® has been researched and developed to support healthy NF-kB levels and activity, which, in turn, helps support a healthy
and appropriate inflammatory response. As a result, ParActin® is suitable for
dietary supplements that support the following condition-specific areas:
• Joint Health
• Healthy Bones
• Healthy Cartilage
• Sports Recovery/Muscle Function
• Healthy Inflammatory Response
• Overall Immune Function
7
Keep Moving! Joint, Bone & Muscle Health for Everybody
Typically, most people think about bone and joint health as a concern for the
elderly. However, individuals who are younger and love being fit can benefit
tremendously from taking a daily supplement with ParActin® to aid flexibility
and mobility, ease joint flare-ups, support healthy muscles, set the stage for increasing fitness goals or just have fun. Further, ParActin® is a great choice for
those at any age who are dead-set on leaving their couch potato days behind.
Intense physical activity can create an undesirable inflammatory response,
which in time, impacts joints through swelling and discomfort, causing muscle
tearing and increased injury. It would seem somewhat antithetical to exercise
for fitness but encounter joints that scream, “Time out!”
However, over-expression of inflammation response figures prominently
in joint issues and, to a certain extent, muscle pain from overuse. Therefore,
doesn’t it make sense to take control by flipping off that master switch? This is
where ParActin® comes in and the numerous clinical research trials and patents that demonstrate its power.
8
ParActin®: Healthy Joint Support
ParActin® inhibits NF-kB activity and reduces the DNA binding of NF-kB,
thereby reducing pro-inflammatory cytokines and enzymes such as COX-2
and prostaglandin that cause pain and inflammation in the body (2). In vitro
research has shown ParActin® to be a natural COX-2 inhibitor without causing
stomach discomfort or increased risk of heart attack and stroke in users.
Rheumatoid arthritis (RA) results from the immune system mistakenly
attacking healthy joints for a prolonged period of time, causing a great deal of
inflammation. Individuals with RA typically have high levels of C-reactive protein (CRP), which is involved in acute and chronic inflammatory activity in unhealthy joints. Rheumatoid factors (RFs) are antibodies detectable in the blood
of approximately 80% of adults with RA. RFs are produced by an immune
system that can attack healthy tissue in your body. Tumor necrosis factor-alpha
(TNF-α), another key driver of inflammation, is a cytokine that stimulates an
acute reaction. Research has found TNF-α to be present in the synovial fluid
of RA patients. Andrographolide is known to reduce TNF-α, which leads to a
significant reduction in RFs.
9
In a 2009 randomized, double-blind and placebo-controlled study published in Clinical Rheumatology, 60 individuals with compromised joints were
given 100 mg of ParActin® or placebo in conjunction with methotrexate (MTX),
three times a day for 14 weeks (3). MTX, a standard therapy for RA, improves
the number of tender and swollen joints, pain and functional status, but longterm use of MTX may cause serious infection and liver damage.
ParActin® was effective in reducing the number and total grade of swollen
joints, the number and total grade of tender joints, as well as improving scores
on HAQ-52, and SF-36 health questionnaires. Its effect was associated with a
reduction of RF, creatine kinase, IgA-RF and IgM-RF. IgA and IgM are antibodies made by the body’s immune system in response to a foreign substance
attack such as bacteria, viruses and fungus. Patients with RA typically have
elevated levels of RF, IgA-RF, IgM-RF and CRP. The reduction in IgA-RF and
IgM-RF is beneficial because their excess is positively correlated with cartilage
damage.
The ParActin® group showed significant improvement compared to the
placebo (with MTX) group in the following scores (see Figure 4):
• Number of swollen joints: nine in the ParActin® group versus 13 in the
placebo group
• Total grade of swollen joints: 11 in the
ParActin® group versus 16 in the placebo group
• Total grade of tender joints: 14 in the
ParActin® group versus 17 in the placebo group
• HAQ: 19 in the ParActin® group versus 24 in the placebo group
• Reduction of RF: 119 in the ParActin® group versus 130 in the placebo
group
• Reduction in IgA: 293.7 in the ParActin® versus 335 in the placebo
group
The study concluded that ParActin® is significantly effective at reducing
symptoms and serological parameters and therefore is useful as a complementary natural treatment for rheumatoid arthritis.
In another human clinical trial published in Innovative Rheumatology, eight
individuals with various rheumatoid conditions were given 300 mg of ParActin®
daily for four years (4). Supplementation with ParActin® showed significant im-
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Figure 4: Effect of Andrographolide on Joint Comfort Over Time versus Placebo. Table
depicts number of patients at risk per group over time. Adapted from Burgos et al. (3).
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provements in the number of swollen joints, total grade of swollen joints, total
grade of tender joints and quality of life.
Also noted were significant reductions in RF, erythrocytes sedimentation
rate and CRP. Furthermore, serum immunological parameters of inflammation
were reduced progressively during 48 months of ParActin® supplementation
(see Figure 5a).
ParActin® may also have additional therapeutic effects over prednisone
and MTX in easing pain and fatigue. Research suggests that Andrographolide
inhibits the COX-2 enzyme and reduces prostaglandin production tied to pain
and inflammation (see Figure 5b).
After 24 months of taking ParActin®, six individuals progressed to supplementing with ParActin® as their only therapeutic. No side effects were observed, indicating ParActin® was safe, nontoxic and well tolerated (4) (see
Figure 5c).
12
Figure 5: Effect of ParActin® in Patients with Chronic Rheumatoid Arthritis.
Adapted from Hildalgo et al. (4).
Stiffness (SF-36 scale) Scale 1-4
Erythrocytes Sedimentation Rate
(ESR-mm/h)
Figure 5a
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Months
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Rheumatoid Factor (UI/L)
Figure 5b
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Figure 5c
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Pain (EVA scale)
Fatigue (EVA scale)
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13
ParActin®: Healthy Bone Support
Fluid, comfortable movement isn’t only the job of the joints. It requires bones
strong enough to withstand bursts of physical activity or prolonged routine
movement.
Healthy bones require two coordinated actions: bone formation (by osteoblasts) and bone reabsorption (by osteoclasts). In the process of bone
formation, osteoblasts produce a calcium and phosphate-based mineral that
is deposited into bones. Almost the entire bone matrix is mineralized by the
osteoblasts. An osteoclast is a type of bone cell that resorbs or breaks down
bone tissue (see Figure 6). However, this healthy balance of bone formation
and bone resorption tends to decline with age, particularly in postmenopausal
women. Osteoporosis is the most common bone disorder and is caused by
excessive bone resorption by osteoclasts without adequate bone formation
by osteoblasts. Increased bone resorption, among other actions, are predominantly caused by the decline of estrogen production in postmenopausal
women, who tend to develop porous bones more often than aging men.
ParActin® has been shown to help support healthy bone function. In research published in the International Journal of Molecular Sciences, a group of
mice whose skeletons mimic postmenopausal osteoarthritis were treated with
Figure 6: Osteoclast and Osteoblast
Osteoclasts have the function
to disrupt the old bone tissue
A proper balance between
osteoclasts and osteoblasts
is the basis for a normal
bone density
OSTEOCLAST
OSTEOBLAST
A hyperactivity of
osteoclasts is
one of the causes
of the onset osteoporosis
Osteoblasts have the function
to produce the new bone tissue
14
NF-kB activation is essential for RANKL (i.e., receptor activator of NF-kB
ligand)-induced osteoclast formation. Andrographolide found in ParActin® —a
natural NF-kB inhibitor—significantly decreased osteoclast formation in the
bone marrow via suppression of RANKL, which are responsible for making
osteoclasts (see Figure 8).
Figure 7: Micro-CT Scanned 3D Image of Mice Tibias Showing that Andrographolide Inhibits
OVX-induced Bone Loss Compared to Vehicle. Adapted from T. Wang et al. (5).
Sham
OVX + Vehicle
OVX + AP 1mg/kg OVX + AP 5mg/kg
RANKL (-)
RANKL (+)
RANKL + AP (5μM)
RANKL + AP (1μM)
RANKL + AP (10μM)
RANKL + AP (10μM)
400
350
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100
50
0
0
1
15
5
10
AP (μM)
TRAP + osteoclast number
Figure 8: Effect of Andrographolide on Osteoclasts. Adapted from T. Wang et al. (5).
TRAP + osteoclast number
5μM)
Andrographolide (5). The use of these ovariectomized (OVX) animals is a typical experimental model for the investigation of postmenopausal osteoporosis
due to estrogen deficiency in women. The ParActin® group showed a significant increase in bone mass, trabecular thickness and number, and a decrease
in trabecular separation compared to control mice (see Figure 7).
400
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100
50
0
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The authors concluded that Andrographolide inhibits estrogen deficiency-induced bone loss in mice and may have supplemental potential for osteoarthritis.
In an in vitro study published in the European Journal of Pharmacology,
Andrographolide from ParActin® inhibited nuclear factors of activated
T-cells (NFAT) activity, which regulates the expression of osteoclast genes and
is linked to bone erosion (6). In another unpublished study, Andrographolide
induced osteoblast mineralization via COX-2 expression, showing a mineralizing effect on the bones with the increase of calcium deposits, thereby suggesting that ParActin® may have other supplemental effects for osteoarthritis (see
Figure 9).
Figure 9: Effect of Andrographolide on Calcium Deposits. Adapted from M.D. Carretta et al. (6).
16
Figure 10: Joint Anatomy and Cartilage Degradation
Synovial membrane
Synovialcytes
Inflammatory cells
T-cells
B-cells
Macrophages
Cartilage degradation and Joint destruction
Chondrocytes
Osteoblasts
TIMPs
Wnts
Hypertrophic chondrocytes
RANK-L
MMPs
Aggracanases
IL-1,6,X
TNF-α
RANK-L/OPG and cathepsin K
Osteoclasts
Articular cartilage
Calcified cartilage and tidemark
Cartilage Bone turnover and bone loss
Bone
ParActin®: Healthy Cartilage Support
Osteoarthritis is characterized by progressive and permanent cartilage degradation. Cartilage erosion can cause inflammation and pain, decreased mobility
and reduced athletic performance (see Figure 10).
This degradation is caused by Interleukin-1β (IL-1β) cytokines, which trigger the over-production of cartilage-degrading enzymes called matrix metalloproteinases (MMPs) in the synovial cells and the chondrocytes. This leads to
a progressive loss of the cartilage matrix, which is composed of biochemicals
aggrecan, hyaluronan (HA) and collagen.
Recent research has shown that Andrographolide inhibits MMPs in
IL-1β-treated human chondrocytes while increasing the natural inhibitors of
these enzymes via the NF-kB pathway. A study published in International
Scholarly Research Notices found that Andrographolide suppressed MMPs
that were induced by IL-1β in equine cartilage (7). Andrographolide further
slows cartilage degradation by dramatically reducing the loss of collagen,
uronic acid, HA and sulfated-glycosaminoglycans (s-GAGs) caused by IL-1β,
a key inducer of cartilage degeneration. The research not only demonstrated
the potent cartilage-protecting activities of Andrographolide, but also showed
17
the ability of Andrographolide to increase the production of cartilage biomolecules including collagen, aggrecan and HA (see Figure 11).
In RA, aggressive fibroblast-like synoviocytes (FLSs) are found in the
synovial tissues. These FLSs invade and destroy joints and cartilage by actively releasing pro-inflammatory cytokines. They also produce massive amounts
of cartilage-degrading enzymes, especially matrix MMPs, which contribute to
the invasive growth of FLSs and subsequent joint destruction.
Researchers at the La Jolla Institute for Allergy and Immunology, in collaboration with colleagues from the University of California, San Diego (UCSD),
identified FLSs as the target of a potential new RA drug that focuses on cells
responsible for the cartilage damage in affected joints. Current RA treatments
focus on intercepting the immune system’s misdirected attack on the lining
of affected joints to alleviate the debilitating symptoms, reduce inflammation
and slow the progression of the disease. “Unfortunately, for around 40% of
patients, immune-targeted therapies are not sufficient to bring them into full
remission,” says the study’s lead author, Nunzio Bottini, M.D., Ph.D., associate
professor at La Jolla Institute and associate professor of medicine at UCSD.
“Even if your inflammation is completely under control with the help of current
therapies—and they are excellent—the damage to the skeletal structure is not
necessarily arrested in the long term because synoviocytes continue to cause
damage,” he explains.
FLSs secrete proteases that digest cartilage, and they also promote osteoclasts differentiation, which in turn attack the bone and generate erosions.
Blocking the action of these synovial fibroblasts will directly protect joints from
cartilage destruction (8).
In a study published in Cell Biology Toxicology, synovial tissues were
collected from 15 RA patients who had undergone a total knee replacement
therapy; the cells were treated with Andrographolide for 48 hours (9). The
study found that Andrographolide induced cell death in these human RA-FLSs
(rheumatoid arthritis fibroblast-like synoviocytes) via cytochrome-C release
and caspase-3 activation, which play key roles in cell death. The author suggests that Andrographolide could be a potential therapeutic in supporting
against joint destruction in both osteoarthritis and RA.
18
s-GAGs level (µ
s-GAGs
300
250
200
150
100
50
0
The remaining content in
cartilage explants (% of control)
s-GAGs level (µg/mL)
300
250
200
Figure 11: Effect of Andrographolide on Cartilage Explants.150
Adapted from S. Tangyuenyong et al. (7)
100
50
400
0
350
HA
The remaining content in
cartilage explants (% of control)
s-GAGs
Control
25 ng/mL IL-1β
IL-1β and 10µM andrographolide
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120
100
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60
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Control
25 ng/mL IL-1β
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Collagen
Uronic acid
Control
25 ng/mL IL-1β
Collagen
Uronic acid
Control
25 ng/mL IL-1β
A condition called synovial hypoxia frequently occurs in patients with RA,
contributing to tendon rupture and perpetual joint destruction. Fifty percent of RA
patients also experience inflammation of the synovial tissue surrounding the tendons, which is associated with multiple ruptures and a poor prognosis for longterm joint function. RA patients often have high levels hypoxia-inducible factor-1
alpha (HIF-1α), a chemical linked to inflammation in the synovial tissues.
In a study published in Life Sciences, synovial tissue was obtained from
50 RA patients during a knee joint arthroscopy (10). The researchers found
that Andrographolide significantly decreased the cartilage-degrading enzymes MMPs, induced by hypoxia. Andrographolide inhibited the migration,
prevented the invasion of RA-FLS and increase of MMPs in RA-FLSs via the
inhibition of HIF-1α signaling. Hypoxia causes RA-FLS migration and invasion.
Andrographolide inhibited hypoxia-induced migration and RA-FLS invasion,
thus suggesting the potential for Andrographolide in benefiting those with joint
degeneration.
19
HA
ParActin®: Muscle Health and Recovery
Muscles are susceptible to damage, just like other bodily tissues. Trauma, infections, certain medications or strenuous exercise can cause varying degrees
of muscle injury. As the saying goes, “No pain, no gain.” But if you’re over the
age of 40, no pain is actually a good thing. If you find yourself in the discomfort
zone, your body may be trying to tell you something.
By the age of 40, the body has endured years of wear and tear, and is
more susceptible to repetitive stress that can cause injury. While you may feel
strong and ready to take on any physical activity, your bones, muscles and
joints could be more delicate than you realize. As we age, our musculoskeletal
system (i.e., bones, joints, tendons, ligaments and muscles) changes by gradually losing muscle mass, connective tissues (i.e., tendons, ligaments, cartilage
and other support structures), flexibility and the resilience that was present at
a younger age. And in addition to the loss of elasticity and resilience, low bone
density conditions such as osteopenia and osteoporosis can further complicate matters.
Skeletal muscle injuries constitute the majority of sports-related injuries.
Injured skeletal muscle undergoes the healing phases of degeneration, inflammation, regeneration and fibrosis (see Figure 12). The body heals damaged
tissue fibers by laying down new soft tissue fibers as part of the secondary
20
Figure 12:
Muscle Laceration Injury
Fibrosis
Degeneration
Inflammation
Proteases
TGF-β1
Growth
Factors
Regeneration 7 days
Regeneration 5 days
phase of the inflammatory process. This occurs in bones, muscles, tendons,
ligaments, joint capsules and cartilage. Healthy new fibers are essential to
healing and pain relief as they replace the torn and damaged ones.
In a pivotal study published in Skeletal Muscle, mdx mice (i.e., mice studied for muscle degeneration and regeneration) were treated with ParActin® for
three months (11). ParActin® was shown to promote muscle health and recovery, making it ideal for those engaged in regular fitness routines, hard labor
or athletic participation. Three positive effects were observed in this study, as
follows:
1. ParActin® reduced inflammation in the skeletal muscle via NF-kB
inhibition. Prostaglandins (PGEs) have been identified and implicated as
major factors in tissue inflammation. Many PGEs are synthesized by cyclooxygenase enzyme and are largely produced during the inflammatory phase
after muscle injury. Aspirin and other NSAIDs inhibit PGE synthesis, and are
typically recommended to be taken in the first few days after injury to limit
inflammation and pain. However, long-term use of these NSAIDs may cause
stomach discomfort. Multiple studies have demonstrated the effectiveness
of selective COX-2 inhibitors in the reduction of joint and muscle pain with
gastrointestinal safety. In the study, supplementation with ParActin® reduced
21
Total NFκB positive nuclei
Figure 13: Effect of ParActin® on NF-kB and COX-2. Adapted from Cabrera et al. (11).
250
200
*
150
*, #
100
50
0
WT
MDX + vehicle
MDX + ParActin®
PAF (100 nM)
ParActin
(150) µM)
COX-2
β-actin
fMLP (100 nM)
ParActin
(150) µM)
COX-2
β-actin
the number of nuclei positive for NF-κB and reduced COX-2 enzyme, which
in turn reduces PGE concentrations that causes pain and inflammation (see
Figure 13).
2. ParActin® reduced fibrosis and pro-fibrotic factor. Transforming
growth factor type beta (TGF-β1) and connective tissue growth factor (CTGF)
have been shown to inhibit skeletal muscle regenerative processes. They
replace scarred connective tissue that is composed of fibronectin, as well as
type-I and type-III collagen. While this fibrotic tissue provides early support for
damaged skeletal muscle, these new fibers do not arrange in the same direction the original fibers were oriented. This results in scarring (fibrosis) in the
injured muscle that often causes stiffness, abnormal joint function, nerve pain
and restricts the regenerative process. Recurring injury and loss of muscle
strength after muscle injuries may be attributable to TGF-ß1–induced fibrosis
within the muscle.
ParActin® administration significantly decreased fibronectin, collagen I and
collagen III levels in the mdx mice. In addition, the ParActin® treatment group
22
CTGF mRNA relativelevels/GAPDH
TGF-β1 mRNA relativelevels/GAPDH
Figure 14: Effect of ParActin® on TGF-β and CTGF. Adapted from Cabrera et al. (11).
8
*
6
4
#
2
0
WT
MDX + vehicle
MDX + ParActin®
15
*
10
*, #
5
0
WT
MDX + vehicle
MDX + ParActin®
saw reduced TGF-β1 and CTGF, two pro-fibrotic factors that contribute to
fibrosis and prevent proper muscle regeneration process. By blocking TGF-ß1
and thus reducing scar tissue, ParActin® can facilitate improved muscle function recovery (see Figure 14).
3. ParActin® reduced muscle damage and lowered serum creatine
kinase. Strenuous exercise and overtraining can lead to structural damage to
muscle cells, triggering white blood cell activity to increase after muscle soreness, thus leading to the inflammatory response. This has been noted especially in marathon runners whose muscle fibers revealed remarkable damage
after both training and marathon competition. The muscle damage causes
calcium to leak out of the muscle, further leading to the activation of enzymes
that break down cellular proteins in the muscle. These proteins then cause an
inflammatory response by the immune system, which then leads to swelling
(water retention at the site of injury) and pain.
23
mN/mm2
Figure 15: Effect of Andrographolide on Muscles. Adapted from Cabrera et al. (11).
In the mdx mouse study, the administration of ParActin® reduced necrosis and
cumulative muscle damage compared with control mdx mice (see Figure 15).
Creatine kinase (CK) is a type of enzyme found within your muscles,
including the heart and brain. Serum CK indicates the overall health of the
muscles within the body and if a serum CK test shows elevated levels, it
indicates muscle strain that may have been caused by simply heavy exercise
or something as serious as a heart attack. Muscle inflammation and other
skeletal muscle damage are associated with an elevated CK level. Depending
upon muscle damage severity, some may have CK levels that are as much
as 100 times normal levels. Serum CK levels were significantly decreased in
ParActin®-treated mdx mice compared with control mdx mice, with an approximately 50% recovery score (see Figure 16).
10000
Figure 17: Effect of ParActin® on Muscles.
Adapted from Cabrera et al. (11).
*
mN/mm2
Serum Creatine Kinase Activity (UI/L)
Figure 16: Effect of Andrographolide on Creatine
Kinase. Adapted from Cabrera et al. (11).
8000
6000
C57 + Vehi
C57 + PAR
mdx + PAR
mdx + Veh
*, #
4000
2000
0
WT
MDX + vehicle
MDX + ParActin®
24
Frequency (pps)
C57 + Vehicle
C57 + PARACTIN®
mdx + PARACTIN®
mdx + Vehicle
50
*
5
30
0
*
20
#
10
id
m
m
dx
dx
+
An
m
dx
dr
og
+
ra
ph
Ve
h
ol
icl
T
e
e
0
W
ol
ra
dr
og
An
+
*
% twitch force, Recovery score = 50.3%
ph
# set backs in the threadmill
e
id
e
icl
Ve
h
+
dx
m
rce, Recovery score = 50.3%
#
% twitch force, Recovery score = 50.3%
% of specific isometric force
*
5
0
% of specific isometric force
#
*
W
W
T
0
W
T
m
dx
+
m Ve
dx hi
m
+ cle
dx
Ve
+
hi
cle
m An
dx dr
+ og
An ra
dr ph
og ol
raide
ph
ol
id
e
0
10
# of set backs, Recovery score = 45.5%
4. ParActin® improved skeletal muscle strength and exercise performance. ParActin®-administrated mdx mice showed improved skeletal muscle
strength and enhanced exercise performance. ParActin®-administrated mdx
mice showed a significant increase in the generation of isometric force (see
Figure 17); an increase twitch and tetanic force in the Tibialis anterior (TA)
muscle (in front of the shin); and a significant decrease in the number of fall
back in the treadmill running protocol, with a recovery score of 45.5% (see
Figure 18).
The author concludes that the supplement group exhibited less severe
muscular dystrophy, performed better in an exercise endurance test and had
improved muscle strength compared to control mdx mice.
25
# set backs in the threadmill
*
50
#
#
10
W
T
m
dx
+
m Ve
dx hi
m
+ cle
dx
Ve
+
hi
cle
m An
dx dr
+ og
An ra
dr ph
og ol
raide
ph
ol
id
e
100
#
15
15
T
100
Peak twitch force (mN/mm2)
150
Peak twitch force (mN/mm2)
150
% Peak tetanic force
% Peak tetanic force
Figure 18: ParActin® Improves Functional Capacity. Adapted from Cabrera et al. (11).
ParActin®: Masters the Immune Balancing Act
Just like the famous Wallenda brothers, when your immune system is balanced and calibrated, it can keep you safe and healthy during times when you
feel like you are walking on a tightrope high above the ground. Stressors—
environmental, mental/emotional and physical—all conspire to hamper the
immune system’s effective functioning, creating an imbalance that may result
in colds, flu and exacerbated allergies. Cold and flu can reach epidemic proportions during the winter months. There are more than 95 million flu cases in
the United States annually, according to the Centers for Disease Control and
Prevention, and more than 62 million cases of the common cold.
When the immune system is balanced and healthy, it launches a series of
events to engage in battle with an invading virus. Interferon gamma plays an
important role in the first line of defense against viral infections; they are part
of the non-specific immune system and are induced at an early stage in viral
infections such as in influenza—before the specific immune system has had
time to respond. Interferon-gamma is produced by certain activated T-cells
and NK cells and is made in response to viral antigens or when stimulated by
26
lymphocytes. Interferons are responsible for reacting to conditions like colds,
fever, shivers, migraines and gastrointestinal disorders. Interferon gamma
interacts with other interleukin molecules such as interleukin-2 and others to
form a complex, lymphokine regulatory network.
Think of it this way, when your immune system is unbalanced, it’s like being
a ship that’s listing to one side or stuck in the doldrums. ParActin® can help
right the ship and move it forward for smooth sailing.
In a randomized, double-blind placebo-controlled study, 109 healthy
students were given either 25 mg per day of ParActin® or placebo for three
months (12). During the first month, there was no significant change between
the groups, evaluated for the presence or absence of common colds. However,
during months two and three, there was significantly less incidence of common
cold in the ParActin® group (30%) compared to the placebo group (62%).
In another randomized, double-blind placebo-controlled study of 158 adults
already with common cold symptoms, 200 mg of ParActin® per day for five
days were shown to significantly decrease the intensity of symptoms compared to the placebo group (13).
According to ParActin® researcher Dr. Juan Hancke, at a low dosage (50
mg), ParActin® stimulates natural defense mechanisms by activating NF-kB,
thereby increases the production of cytokines such as interferon gamma and
interleukin-2 to help boost the immune response in winter. Once an individual
begins to feel under the weather, 300 mg of ParActin® inhibits NF-kB, thereby
reducing the production of pro-inflammatory cytokines such as interferon
gamma and interleukin-2 to help produce a better sense of wellness. The immune and inflammation balancing properties of ParActin® may assist the body
to help fight a viral antigen while reducing the overload of cytokines (14).
27
ParActin®: Organic, Non-GMO, Vegan Choice
Yes, there are quite a few choices out there to keep you healthy and preserve
free movement. Before you reach for the old standby, here’s why ParActin® (a
specialized and patented extract of the abundant herb Andrographis paniculata) may be your best choice.
As a botanical, ParActin® has nothing undesirable in it that typically comes
from bovine or other animal sources (eggshells and seafood shells). As more
and more Americans are discovering they have food sensitivities and/or allergies, ParActin® is a clean ingredient. It is also non-GMO, cultivated without
pesticides (wild-crafted) and also available in an organic version.
ParActin® is attractive for any consumer from vegans to omnivores; there is
no limit to potential consumers. ParActin® is:
• No bovine (chondroitin), BSE-Free
• Shellfish-free (for those concerned about shellfish allergies/vegans)
• Eggshell-free (for those concerned about eggshell allergies/vegans)
• Non-GMO
• Vegan
• Wild-crafted
• Non-irradiated, TSE free
• Certified kosher and halal
• Available in organic and conventional
Botanical Source: Andrographis paniculata
Countries of Origin: India, China, Southeast Asia
Part Used: Stems and leaves
Shelf Life: 3 years
Active Ingredients: Not less than 50% patented extract of bioactive
andrographolides, 14-deoxyandrographolide, neoandrographolide.
Applications: Nutritional supplements targeted for: sports nutrition,
and support of bone, joint, muscle, relief of aches and discomfort, and
immune health.
28
FAQs about HP Ingredients and ParActin®
What claims can be made for ParActin®?
Multiple human clinical studies allow for the following claims:*
• Supports Healthy Inflammatory Response
• Supports Healthy Joint Function
• Strengthens Joints and Eases Joint Flare-ups
• Improves Flexibility and Mobility
• Maintains Bone Mass and Strength
• Supports Muscle Health
• Supports Healthy Immune Response
• Supports Healthy Cartilage
What are the dosage amounts for ParActin®?
Typical dosage recommendations, based on traditional use and on the available scientific evidence in humans, are 300 mg daily, which may be taken in
150 mg doses twice daily. Those seeking optimum support may take as much
as 600 mg daily.
Is ParActin® patented?
Yes. ParActin® has U.S. Patent #8,084,495 B2, Composition and Use: “Composition of Labdane Diterpenes Extracted From Andrographis Paniculata,
Useful For The Treatment Of Autoimmune Diseases, And Alzheimer’s Disease
By Activation of PPAR-Gamma Receptors.”
For joint health, what are the mechanisms or mode of action of ParActin®?
• Inhibits NF-κB binding to DNA
• Inhibits IKKβ
• Inhibits COX-2 and reduces PGE2
• Inhibits NFAT—bone erosion
• Stimulates osteoblasts and calcium deposition
• Decreases Rheumatoid Factor—TNF-α
• Reduces IgA and IgM: cartilage damage
• Reduces C-Reactive Protein
• Promotes regulatory T cell (Treg), CD4+CD25+
• Reduces AP-1 and STAT3 in synovial tissue
29
Where is ParActin® grown and processed?
Andrographis paniculata is widely cultivated in India, China and Southeastern
Asia. ParActin® is sustainably harvested and is processed in a GMP-certified
and ISO 9001-2008-certified Quality Management Systems facility.
Is ParActin® GRAS (Generally Recognized As Safe?)
It is not GRAS for food products, but it is allowed for use in dietary supplements.
Who is HP Ingredients (HPI)?
HP Ingredients (HPI) is a fast-growing research-based botanical company that
offers unique, innovative, science-based, clinically proven, patented, safe and
natural ingredients to the nutraceutical industry. HPI’s ingredients address today’s most common chronic health conditions; they help support optimal joint,
bone and muscle health, as well as testosterone, energy, heart, blood sugar,
cholesterol, weight management, brain and memory health.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to treat, cure or prevent any disease.
What’s HPI’s mission?
HPI was founded in 2001 by Annie Eng with the goal of bringing nature and
science together. Today, HP Ingredients is an innovative nutraceutical company dedicated to providing cutting-edge, science-based nutraceuticals that
addresses cholesterol, blood glucose control, weight management, joint
health, andropause and healthy aging. HPI believes in ongoing research
and development for its premier ingredients. Working with top scientists from
around the world, HPI is dedicated to providing ongoing research on its proprietary ingredients in a qualitative manner similar to pharmaceutical products.
The company believes in supporting its products with proven science, bringing
well-researched, patented plant extracts to the nutraceutical industry.
The material presented in this piece is for industry education only. It is not intended to
serve as medical advice. Dietary supplements do not cure, treat or prevent any diseases.
Join/Sign up: Receive updates and be the first to hear about new
product development, clinical studies, published articles and more.
Click here to join our thousands of industry professionals.
30
References
1.
E. Setiawan et al., “Role of Translocator Protein Density, a Marker of Neuroinflammation,
in the Brain During Major Depressive Episodes,” JAMA Psychiatry 73 (1), 87–88 (2016).
2. M.A. Hidalgo et al., “Andrographolide interferes DNA binding of NF-KB in HL- 60/Neutrophils cells,” Br. J. Pharmacol. 144 (5), 680-686 (2005).
3. R.A. Burgos et al., “Efficacy of an Andrographis paniculata Composition for the Relief of
Rheumatoid Arthritis Symptoms: A Prospective Randomized Placebo-Controlled Trial,”
Clinical Rheumatol. 28 (8), 931–946 (2009).
4. M
. Hidalgo et al., “Andrographolide a New Potential Drug for the Long Term Treatment
of Rheumatoid Arthritis Disease,” Innovative Rheumatology, 256–259 (2013).
5. T
. Wang et al., “Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways,” Int. J. Mol. Sci. 16 (11), 27470–27481 (2015).
6. M.D. Carretta et al., “Andrographolide Reduces IL-2 Production in T-Cells by Interfering
with NFAT and MAPK Activation,” Eur. J. Pharmacol. 602(2-3), 413–421 (2009).
7. S. Tangyuenyong, et al., “Andrographolide Exerts Chondroprotective Activity in Equine
Cartilage Explant and Suppresses Interleukin-1β-Induced MMP-2 Expression in Equine
Chondrocyte Culture,” International Scholarly Research Notices 1–8 (2014).
8. K.M. Doody, et al., “Targeting Phosphatase-Dependent Proteoglycan Switch for Rheumatoid Arthritis Therapy,” Sci. Transl. Med. 7 (288), (2015).
9. J. Yan et al., “Andrographolide Induced Cell Cycle Arrest and Apoptosis in Human
Rheumatoid Arthritis Fibroblast-Like Synoviocytes,” Cell Biol. Toxicol. 28 (1), 47–56
(2012).
10. L. Guo-feng et al., “Andrographolide Inhibits the Migration, Invasion and Matrix Metalloproteinase Expression Of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via Inhibition of HIF-1α Signaling,” Life Sci. 136, 67–72 (2015).
11. D. Cabrera et al., “Andrographolide Attenuates Skeletal Muscle Dystrophy In Mdx Mice
And Increases Efficiency of Cell 3 Therapy by Reducing Fibrosis,”Skelet. Muscle 4 (6),
(2014).
12. D.D. Cáceres et al., “Prevention of Common Colds with Andrographis paniculata Dried
Extract: A Pilot Double Blind Trial,” Phytomed. 4 (2), 101-104 (1997).
13. JL. Hancke et al., “A Double Blind Study with a New Monodrug: Kan Jang Decrease of
Symptoms and Enhancement of Resistance to Common Colds,” Phytother. Res. 9: 559562, 1995.
14. R.A. Burgos et al., “Andrographolide Inhibits Infγ and IL-2 Cytokine Production and
Protects against Cell Apoptosis,” Planta Medica. 71 (5), 429-434 (2005).
31
Glossary of Terms
This eBook is sponsored by
Supplier of
AP-1: Activator protein 1 is involved in cellular proliferation,
transformation and death.
CD4 + CD25: Two types of regulatory T-cells that control
the burst of superantigen-induced cytokine production.
COX-2: Cyclooxygenase-2 is an enzyme responsible for
the formation of prostaglandins, prostacyclins and thromboxanes, which are involved in the inflammatory response.
C-reactive protein: An acute phase reactant, meaning that
its levels will rise in response to inflammation.
IgM and IgA: Immunoglobins M and A are two types of
antibodies in the blood that primarily protect individuals
from infections inside the body’s tissue, organs and blood.
IKKβ: An IRF5 kinase that instigates inflammation.
IL-2: Interleukin-2 is a type of cytokine-signaling molecule
in the immune system and a protein that regulates the
activities of white blood cells that are responsible for
immunity.
IL-6: Interleukin-6 acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine.
NFAT: Nuclear factor of activated T-cells is a general name
applied to a family of transcription factors shown to be
important for immune response.
NF-kB: Nuclear factor-kappa B is a protein complex that
controls transcription of DNA, cytokine production and cell
survival.
PGE2: Prostaglandin E2 is a prostaglandin that ultimately
induces fever. It also suppresses T-cell receptor signaling
and may play a role in the resolution of inflammation.
PPAR-γ: Peroxisome proliferator-activated receptor
gamma is a nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids.
STAT3: Signal transducer and activator of transcription 3 is
a protein-coding gene that has been found to play a fundamental role in converting normal cells to cancerous cells.
Synovial membrane: The soft tissue found between the
articular capsule (joint capsule) and the joint cavity of
synovial joints.
TNF-α: Tumor necrosis factor alpha is a cell-signaling
protein (cytokine) involved in systemic inflammation and
is one of the cytokines that make up the acute phase
reaction.
HP Ingredients Corp.
707 24th Ave. West
Bradenton, FL 34205
Toll-free: (877)437-2234
Tel: (941)749-7066
Fax: (866)278-2874
www.hpingredients.com
[email protected]
Key Personnel
Annie Eng, President
Hame K. Persaud, Executive Vice President
Dr. Juan Hancke, Chief Scientific Director
This publication is brought to you by WholeFoods Magazine. For more information, see www.hpingredients.com.
Copyright ©2016. All rights reserved. WHOLE FOODS
(ISSN 0193-1504) (USPS 405-710) is published monthly,
with May Source Directory issue, in the interest of the
health/natural products industry by WHOLE FOODS
Magazine, WFC, Inc., 51 Cragwood Road, Ste. 100, South
Plainfield, NJ 07080, telephone (908)769-1160, FAX
(908)769-1171. WholeFoodsMAGAZINE has no affiliation
with Whole Foods Market. WholeFoodsMAGAZINE is
published by WFC, Inc.

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