Curcumin as a potent and selective inhibitor of 11?-hydroxysteroid dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats.

ABSTRACT:

Background

11?-Hydroxysteroid dehydrogenase 1 (11?-HSD1) activates glucocorticoid locally in liver and fat tissues to aggravate metabolic syndrome. 11?-HSD1 selective inhibitor can be used to treat metabolic syndrome. Curcumin and its derivatives as selective inhibitors of 11?-HSD1 have not been reported.

Methodology

Curcumin and its 12 derivatives were tested for their potencies of inhibitory effects on human and rat 11?-HSD1 with selectivity against 11?-HSD2. 200 mg/kg curcumin was gavaged to adult male Sprague-Dawley rats with high-fat-diet-induced metabolic syndrome for 2 months.

Results and conclusions

Curcumin exhibited inhibitory potency against human and rat 11?-HSD1 in intact cells with IC50 values of 2.29 and 5.79 µM, respectively, with selectivity against 11?-HSD2 (IC50, 14.56 and 11.92 µM). Curcumin was a competitive inhibitor of human and rat 11?-HSD1. Curcumin reduced serum glucose, cholesterol, triglyceride, low density lipoprotein levels in high-fat-diet-induced obese rats. Four curcumin derivatives had much higher potencies for Inhibition of 11?-HSD1. One of them is (1E,4E)-1,5-bis(thiophen-2-yl) penta-1,4-dien-3-one (compound 6), which had IC50 values of 93 and 184 nM for human and rat 11?-HSD1, respectively. Compound 6 did not inhibit human and rat kidney 11?-HSD2 at 100 µM. In conclusion, curcumin is effective for the treatment of metabolic syndrome and four novel curcumin derivatives had high potencies for inhibition of human 11?-HSD1 with selectivity against 11?-HSD2.

SUBMITTER: Hu GX 

PROVIDER: S-EPMC3606385 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature