Identification of matrine as a promising novel drug for hepatic steatosis and glucose intolerance with HSP72 as an upstream target
文献类型：期刊论文
| 作者 | Zeng, Xiao-Yi2,3; Wang, Hao2,3; Bai, Fang1; Zhou, Xiu2,3; Li, Song-Pei2,3; Ren, Lu-Ping2,3; Sun, Ruo-Qiong2,3; Xue, Charlie C. L.2,3; Jiang, Hua-Liang1 ; Hu, Li-Hong1
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| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2015-09 |
| 卷号 | 172期号:17页码:4303-4318 |
| ISSN号 | 0007-1188 |
| DOI | 10.1111/bph.13209 |
| 文献子类 | Article |
| 英文摘要 | Background and PurposeMatrine is a small molecule drug used in humans for the treatment of chronic viral infections and tumours in the liver with little adverse effects. The present study investigated its therapeutic efficacy for insulin resistance and hepatic steatosis in high-fat-fed mice. Experimental ApproachC57BL/J6 mice were fed a chow or high-fat diet for 10 weeks and then treated with matrine or metformin for 4 weeks. The effects on lipid metabolism and glucose tolerance were evaluated. Key ResultsOur results first showed that matrine reduced glucose intolerance and plasma insulin level, hepatic triglyceride content and adiposity in high-fat-fed mice without affecting caloric intake. This reduction in hepatosteatosis was attributed to suppressed lipid synthesis and increased fatty acid oxidation. In contrast to metformin, matrine neither suppressed mitochondrial respiration nor activated AMPK in the liver. A computational docking simulation revealed HSP90, a negative regulator of HSP72, as a potential binding target of matrine. Consistent with the simulation results, matrine, but not metformin, increased the hepatic protein level of HSP72 and this effect was inversely correlated with both liver triglyceride level and glucose intolerance. Conclusions and ImplicationsTaken together, these results indicate that matrine may be used for the treatment of type 2 diabetes and hepatic steatosis, and the molecular action of this hepatoprotective drug involves the activation of HSP72 in the liver. |
| WOS关键词 | FATTY LIVER-DISEASE ; INDUCED INSULIN-RESISTANCE ; HSP90 MOLECULAR CHAPERONE ; HEAT-SHOCK ; CONCISE GUIDE ; IN-VIVO ; ARRIVE GUIDELINES ; PPAR-GAMMA ; CELL-DEATH ; PHARMACOLOGY |
| 资助项目 | National Health and Medical Research Council of Australia[535921] ; Australian Research Council[DP 11010396] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000359295200007 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276424]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Ye, Ji-Ming |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 2.RMIT Univ, Hlth Innovat Res Inst, Lipid Biol & Metab Dis, Melbourne, Vic, Australia; 3.RMIT Univ, Sch Hlth Sci, Melbourne, Vic, Australia; |
| 推荐引用方式 GB/T 7714 | Zeng, Xiao-Yi,Wang, Hao,Bai, Fang,et al. Identification of matrine as a promising novel drug for hepatic steatosis and glucose intolerance with HSP72 as an upstream target[J]. BRITISH JOURNAL OF PHARMACOLOGY,2015,172(17):4303-4318. |
| APA | Zeng, Xiao-Yi.,Wang, Hao.,Bai, Fang.,Zhou, Xiu.,Li, Song-Pei.,...&Ye, Ji-Ming.(2015).Identification of matrine as a promising novel drug for hepatic steatosis and glucose intolerance with HSP72 as an upstream target.BRITISH JOURNAL OF PHARMACOLOGY,172(17),4303-4318. |
| MLA | Zeng, Xiao-Yi,et al."Identification of matrine as a promising novel drug for hepatic steatosis and glucose intolerance with HSP72 as an upstream target".BRITISH JOURNAL OF PHARMACOLOGY 172.17(2015):4303-4318. |
入库方式： OAI收割
来源：上海药物研究所
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