Emodin, a natural product, selectively inhibits 11 beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice
文献类型：期刊论文
| 作者 | Feng, Ying; Huang, Su-Ling ; Dou, Wei; Zhang, Song; Chen, Jun-Hua; Shen, Yu; Shen, Jian-Hua; Leng, Ying
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| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2010-09 |
| 卷号 | 161期号:1页码:113-126 |
| 关键词 | emodin 11 beta-hydroxysteroid dehydrogenase type 1 diet-induced obese mice insulin resistance metabolic syndrome type 2 diabetes |
| ISSN号 | 0007-1188 |
| DOI | 10.1111/j.1476-5381.2010.00826.x |
| 文献子类 | Article |
| 英文摘要 | BACKGROUND AND PURPOSE 11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-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 11 beta-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 11 beta-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 11 beta-HSD1 inhibitor with the IC50 of 186 and 86 nM for human and mouse 11 beta-HSD1, respectively. Single oral administration of emodin inhibited 11 beta-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 11 beta-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 11 beta-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. |
| WOS关键词 | HEPATIC INSULIN SENSITIVITY ; HUMAN ADIPOSE-TISSUE ; IN-VIVO ; GLUCOSE-TOLERANCE ; VISCERAL OBESITY ; CARBENOXOLONE ; GLUCOCORTICOIDS ; DEXAMETHASONE ; RESISTANCE ; GENE |
| 资助项目 | National Basic Research Program of China[2009CB522300] ; National Nature Science Foundation of China[30873106] ; Shanghai Rising-Star Foundation[08QH14028] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program', China[2009ZX09103-061] ; Science and Technology Commission of Shanghai Municipality[08DZ1980200] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000281061900009 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278784]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Leng, Ying |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Feng, Ying,Huang, Su-Ling,Dou, Wei,et al. Emodin, a natural product, selectively inhibits 11 beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice[J]. BRITISH JOURNAL OF PHARMACOLOGY,2010,161(1):113-126. |
| APA | Feng, Ying.,Huang, Su-Ling.,Dou, Wei.,Zhang, Song.,Chen, Jun-Hua.,...&Leng, Ying.(2010).Emodin, a natural product, selectively inhibits 11 beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice.BRITISH JOURNAL OF PHARMACOLOGY,161(1),113-126. |
| MLA | Feng, Ying,et al."Emodin, a natural product, selectively inhibits 11 beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice".BRITISH JOURNAL OF PHARMACOLOGY 161.1(2010):113-126. |
入库方式： OAI收割
来源：上海药物研究所
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