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Emodin, a natural product, selectively inhibits 11β‐hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet‐induced obese mice
Author(s) -
Feng Ying,
Huang Suling,
Dou Wei,
Zhang Song,
Chen Junhua,
Shen Yu,
Shen Jianhua,
Leng Ying
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00826.x
Subject(s) - emodin , insulin resistance , 11β hydroxysteroid dehydrogenase type 1 , endocrinology , medicine , metabolic syndrome , pharmacology , chemistry , biology , insulin , biochemistry , dehydrogenase , diabetes mellitus , enzyme
BACKGROUND AND PURPOSE 11β‐Hydroxysteroid dehydrogenase type 1 (11β‐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 11β‐HSD1 and its ability to ameliorate metabolic disorders in diet‐induced obese (DIO) mice. EXPERIMENTAL APPROACH Scintillation proximity assay was performed to evaluate inhibition of emodin against recombinant human and mouse 11β‐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. KEY RESULTS Emodin is a potent and selective 11β‐HSD1 inhibitor with the IC 50 of 186 and 86 nM for human and mouse 11β‐HSD1, respectively. Single oral administration of emodin inhibited 11β‐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 11β‐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 AND IMPLICATIONS This study demonstrated a new role for emodin as a potent and selective inhibitor of 11β‐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.