tema 6. curcuminoides estructura - uvatetrahydrocurcumin is more effective than curcuminin...
TRANSCRIPT
![Page 1: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/1.jpg)
Tema 6. Curcuminoides
EstructuraSimilitud con otras biomoléculas naturalesBiodisponibilidadEfectos molecularesMetabolismo
![Page 2: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/2.jpg)
![Page 3: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/3.jpg)
O O
H3CO
HO
OCH3
OH
curcumina
![Page 4: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/4.jpg)
Aggarwal BB.Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
![Page 5: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/5.jpg)
T. Girbés
P. Anand et al., Biochem. Pharmacol. 76, 1590‐1611 (2008)
![Page 6: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/6.jpg)
Aggarwal BB.Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
![Page 7: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/7.jpg)
T. Girbés
P. Anand et al., Mol. Pharm., 4, 807‐818 (2007) BIODISPONIBILIDAD
HPLC HPLC
1 h5 mg piperine 2 g
![Page 8: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/8.jpg)
T. Girbés
P. Anand et al., Mol. Pharm., 4, 807‐818 (2007)
![Page 9: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/9.jpg)
![Page 10: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/10.jpg)
DMC (20 μM)
vehicle (0.1% DMSO) NGF (50 ng/ml)
curcumin (10 μM) curcumin (20 μM)
DMC (10 μM)
J Agric Food Chem. 2011 Dec 6. [Epubahead of print]
Curcuminoids Promote Neurite Outgrowthin PC12 Cells through MAPK/ERK‐ and PKC‐Dependent Pathways.
Liao KK, WuMJ, Chen PY, Huang SW, ChiuSJ, Ho CT, Yen JH.(Taiwan, USA)
demethoxycurcumin (DMC) bisdemethoxycurcumin (BDMC)
![Page 11: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/11.jpg)
![Page 12: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/12.jpg)
![Page 13: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/13.jpg)
T. Girbés
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)
![Page 14: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/14.jpg)
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
![Page 15: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/15.jpg)
T. Girbés
V. Calabrese et al., Mol. Nutr. Food Res. 52, 1062‐1073 (2008)
Vitagenes: genes quecodifican “heat shock
proteins” (Hsp) Hsp32, Hsp70,
thioredoxin y sirtuina
![Page 16: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/16.jpg)
T. Girbés
V. Calabrese et al., Mol. Nutr. Food Res. 52, 1062‐1073 (2008)
Vitagenes: genes quecodifican “heat shock
proteins” (Hsp) Hsp32, Hsp70,
thioredoxin y sirtuina(nuclear factor kappa‐light‐chain‐enhancer of activated B cells)
![Page 17: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/17.jpg)
![Page 18: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/18.jpg)
monocyte chemotacticprotein‐1
![Page 19: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/19.jpg)
![Page 20: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/20.jpg)
![Page 21: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/21.jpg)
T. Girbés
P. Anand et al., Mol. Pharm., 4, 807‐818 (2007)
![Page 22: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/22.jpg)
![Page 23: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/23.jpg)
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 beendemonstrated to be anti‐cancerogenic and anti‐angiogenic and prevents type II diabetes. Inthis present study, we investigated the chemopreventive effects and underlying molecularmechanisms of dietary administration of CUR and THC in azoxymethane (AOM)‐inducedcolon 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 chemopreventiveefficacy and molecular mechanisms of dietary THC against AOM‐induced colonic tumorigenesis.
Mol. Nutr. Food Res. 2011, 55, 1819–1828
![Page 24: Tema 6. Curcuminoides Estructura - UVaTetrahydrocurcumin is more effective than curcuminin preventing azoxymethane‐induced colon Carcinogenesis. Ching‐Shu Lai y cols. Tetrahydrocurcumin(THC),](https://reader033.vdocuments.us/reader033/viewer/2022041812/5e588890f5238d751f299c92/html5/thumbnails/24.jpg)