title: Curcumin as a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats.
abstract: BACKGROUND
  11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) activates glucocorticoid locally in liver and fat tissues to aggravate metabolic syndrome. 11β-HSD1 selective inhibitor can be used to treat metabolic syndrome. Curcumin and its derivatives as selective inhibitors of 11β-HSD1 have not been reported.
  
  
  METHODS
  Curcumin and its 12 derivatives were tested for their potencies of inhibitory effects on human and rat 11β-HSD1 with selectivity against 11β-HSD2. 200 mg/kg curcumin was gavaged to adult male Sprague-Dawley rats with high-fat-diet-induced metabolic syndrome for 2 months.
  
  
  CONCLUSIONS
  Curcumin exhibited inhibitory potency against human and rat 11β-HSD1 in intact cells with IC50 values of 2.29 and 5.79 µM, respectively, with selectivity against 11β-HSD2 (IC50, 14.56 and 11.92 µM). Curcumin was a competitive inhibitor of human and rat 11β-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 11β-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 11β-HSD1, respectively. Compound 6 did not inhibit human and rat kidney 11β-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 11β-HSD1 with selectivity against 11β-HSD2.
authors.affiliation: School of Pharmacy, Wenzhou Medical College, Wenzhou, China.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
authors.forename: Han
authors.initials: H
authors.lastname: Lin
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Lian
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Zhou
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhou
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008861:Microsomes / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003474:Curcumin