Tema 6. Curcuminoides Estructura Similitud con otras biomoléculas

Tema 6. Curcuminoides
Estructura
Similitud con otras biomoléculas naturales
Biodisponibilidad
Efectos moleculares
Metabolismo O
O
H3CO
OCH3
HO
OH
curcumina
Aggarwal BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
P. Anand et al., Biochem. Pharmacol. 76, 1590‐1611 (2008) T. Girbés
Aggarwal BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
P. Anand et al., Mol. Pharm., 4, 807‐818 (2007) 1 h
HPLC
BIODISPONIBILIDAD
5 mg piperine
HPLC
T. Girbés
2 g P. Anand et al., Mol. Pharm., 4, 807‐818 (2007) T. Girbés
vehicle (0.1% DMSO) NGF (50 ng/ml)
J Agric Food Chem. 2011 Dec 6. [Epub
ahead of print]
Curcuminoids Promote Neurite Outgrowth
in PC12 Cells through MAPK/ERK‐ and PKC‐
Dependent Pathways.
curcumin (10 μM) curcumin (20 μM)
Liao KK, Wu MJ, Chen PY, Huang SW, Chiu
SJ, Ho CT, Yen JH.
(Taiwan, USA)
demethoxycurcumin (DMC) bisdemethoxycurcumin (BDMC)
DMC (10 μM) DMC (20 μM)
V. Calabrese et al., Mol. Nutr. Food Res. 52, 1062‐1073 (2008)
Nuclear factor (erythroid‐derived 2)‐like 2, NFE2L2 o Nrf2
(induce la expresión de diversos genes) T. Girbés
BLANCOS DE Nrf2
NAD(P)H quinone oxidoreductase 1 (Nqo1), reducción de quinonas causantes de estrés oxidativo Glutamate‐cysteine ligase, síntesis de glutatión (GSH)
Glutathione S‐transferase (GST), conjugación de GSH con xenobióticos electrófilos endógenos Heme oxygenase‐1 (HMOX1, HO‐1), cataliza la rotura del grupo hemo produciendo biliverdina CO2 y Fe (sepsis, hipertension, ateroesclerosis, daño pulmonar agudo, daño renal, dolor) UDP‐glucuronosyltransferase (UGT), cataliza la conjugación de ácido glucurónico con substratos endógenos y exógenos (bilirrubina; acetaminofeno)
Multidrug resistance‐associated proteins (Mrps), transportadores de eflujo de drogas para excreción en heces y orina V. Calabrese et al., Mol. Nutr. Food Res. 52, 1062‐1073 (2008)
Vitagenes: genes que
codifican “heat shock proteins” (Hsp) Hsp32, Hsp70, thioredoxin y sirtuina
T. Girbés
V. Calabrese et al., Mol. Nutr. Food Res. 52, 1062‐1073 (2008)
(nuclear factor kappa‐
light‐chain‐enhancer of activated B cells) T. Girbés
Vitagenes: genes que
codifican “heat shock proteins” (Hsp) Hsp32, Hsp70, thioredoxin y sirtuina
monocyte chemotactic
protein‐1
P. Anand et al., Mol. Pharm., 4, 807‐818 (2007) T. Girbés
Mol. Nutr. Food Res. 2011, 55, 1819–1828
Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR), has been
demonstrated to be anti‐cancerogenic and anti‐angiogenic and prevents type II diabetes. In
this present study, we investigated the chemopreventive effects and underlying molecular
mechanisms of dietary administration of CUR and THC in azoxymethane (AOM)‐induced
colon carcinogenesis in mice. We found that dietary administration of both CUR and THC could reduce aberrant crypt foci and polyps formation, while THC showed a better inhibitory effect than CUR. At the molecular level, results from Western blot analysis and immunohistochemistry staining showed that dietary CUR and THC exhibited anti‐inflammatory activity by decreasing the levels of inducible NOS and COX‐2 through downregulation of ERK1/2 activation. In addition, both dietary CUR and THC significantly decreased AOM‐induced Wnt‐1 and b‐catenin protein expression, as well as the phosphorylation of GSK‐3b in colonic tissue. Moreover, dietary feeding with CUR and THC markedly reduced the protein level of connexin‐43, an important molecule of gap junctions, indicating that both CUR and THC might interfer with the intercellular communication of crypt cells.
Taken together, these results demonstrated for the first time the in vivo chemopreventive
efficacy and molecular mechanisms of dietary THC against AOM‐induced colonic tumorigenesis.