Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice.
OBJECTIVE
11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an attractive therapeutic target of type 2 diabetes and metabolic syndrome. Emodin, a natural product and active ingredient of various Chinese herbs, has been demonstrated to possess multiple biological activities. Here, we investigated the effects of emodin on 11beta-HSD1 and its ability to ameliorate metabolic disorders in diet-induced obese (DIO) mice.


METHODS
Scintillation proximity assay was performed to evaluate inhibition of emodin against recombinant human and mouse 11beta-HSDs. The ability of emodin to inhibit prednisone- or dexamethasone-induced insulin resistance was investigated in C57BL/6J mice and its effect on metabolic abnormalities was observed in DIO mice.


RESULTS
Emodin is a potent and selective 11beta-HSD1 inhibitor with the IC(50) of 186 and 86 nM for human and mouse 11beta-HSD1, respectively. Single oral administration of emodin inhibited 11beta-HSD1 activity of liver and fat significantly in mice. Emodin reversed prednisone-induced insulin resistance in mice, whereas it did not affect dexamethasone-induced insulin resistance, which confirmed its inhibitory effect on 11beta-HSD1 in vivo. In DIO mice, oral administration of emodin improved insulin sensitivity and lipid metabolism, and lowered blood glucose and hepatic PEPCK, and glucose-6-phosphatase mRNA.


CONCLUSIONS
This study demonstrated a new role for emodin as a potent and selective inhibitor of 11beta-HSD1 and its beneficial effects on metabolic disorders in DIO mice. This highlights the potential value of analogues of emodin as a new class of compounds for the treatment of metabolic syndrome or type 2 diabetes.
Feng
Ying
Y
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
Huang
Su-ling
SL
Dou
Wei
W
Zhang
Song
S
Chen
Jun-hua
JH
Shen
Yu
Y
Shen
Jian-hua
JH
Leng
Ying
Y
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000305:Adrenal Cortex Hormones / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000633:toxicity; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009765:Obesity; D011241:Prednisone / Q000633:toxicity; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D047428:Protein Kinase Inhibitors; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D004642:Emodin; D011241:Prednisone