Tema 6. Curcuminoides. Estructura Similitud con otras biomoléculas naturales Biodisponibilidad Efectos moleculares Metabolismo

Transcription

1 Tema 6. Curcuminoides Estructura Similitud con otras biomoléculas naturales Biodisponibilidad Efectos moleculares Metabolismo

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3 O O H 3 CO OCH 3 HO curcumina OH

4 Aggarwal BB. Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

5 P. Anand et al., Biochem. Pharmacol. 76, (2008) T. Girbés

6 Aggarwal BB. Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

7 P. Anand et al., Mol. Pharm., 4, (2007) BIODISPONIBILIDAD 1 h 5 mg piperine 2 g HPLC HPLC T. Girbés

8 P. Anand et al., Mol. Pharm., 4, (2007) T. Girbés

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10 vehicle (0.1% DMSO) curcumin (10 μm) NGF (50 ng/ml) curcumin (20 μm) J Agric Food Chem Dec 6. [Epub ahead of print] Curcuminoids Promote Neurite Outgrowth in PC12 Cells through MAPK/ERK and PKC Dependent Pathways. Liao KK, Wu MJ, Chen PY, Huang SW, Chiu SJ, Ho CT, Yen JH. (Taiwan, USA) DMC (10 μm) DMC (20 μm) demethoxycurcumin (DMC) bisdemethoxycurcumin (BDMC)

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13 V. Calabrese et al., Mol. Nutr. Food Res. 52, (2008) Nuclear factor (erythroid derived 2) like 2, NFE2L2 o Nrf2 (induce la expresión de diversos genes) T. Girbés

14 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

15 V. Calabrese et al., Mol. Nutr. Food Res. 52, (2008) Vitagenes: genes que codifican heat shock proteins (Hsp) Hsp32, Hsp70, thioredoxin y sirtuina T. Girbés

16 V. Calabrese et al., Mol. Nutr. Food Res. 52, (2008) (nuclear factor kappalight chain enhancer of activated B cells) Vitagenes: genes que codifican heat shock proteins (Hsp) Hsp32, Hsp70, thioredoxin y sirtuina T. Girbés

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18 monocyte chemotactic protein 1

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21 P. Anand et al., Mol. Pharm., 4, (2007) T. Girbés

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23 Mol. Nutr. Food Res. 2011, 55, 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.

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