Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-gamma and PPAR-alpha agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice
文献类型：期刊论文
| 作者 | Feng, Li1,5; Luo, Huan4; Xu, Zhijian3 ; Yang, Zhuo3; Du, Guoxin1; Zhang, Yu5; Yu, Lijing5; Hu, Kaifeng4; Zhu, Weiliang3; Tong, Qingchun2
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| 刊名 | DIABETOLOGIA
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| 出版日期 | 2016-06 |
| 卷号 | 59期号:6页码:1276-1286 |
| ISSN号 | 0012-186X |
| 关键词 | Alternative binding site Bavachinin Canonical ligand-binding pocket Carbohydrate metabolism Lipid metabolism Pan-PPAR agonist Synergistic effects |
| DOI | 10.1007/s00125-016-3912-9 |
| 文献子类 | Article |
| 英文摘要 | Aims/hypothesis Pan-peroxisome proliferator-activated receptor (PPAR) agonists have long been sought as therapeutics against the metabolic syndrome, but current PPAR agonists show limited efficacy and adverse effects. Natural herbs provide a structurally untapped resource to prevent and treat complicated metabolic syndrome. Methods Natural PPAR agonists were screened using reporter gene, competitive binding and 3T3-L1 pre-adipocyte differentiation assays in vitro. The effects on metabolic phenotypes were verified in db/db and diet-induced obese mice. In addition, potentially synergistic actions of bavachinin (BVC, a novel natural pan-PPAR agonist from the fruit of the traditional Chinese glucose-lowering herb malaytea scurfpea) and synthetic PPAR agonists were studied through nuclear magnetic resonance, molecular docking, reporter gene assays and mouse studies. Results BVC exhibited glucose-lowering properties without inducing weight gain and hepatotoxicity. Importantly, BVC synergised with thiazolidinediones, which are synthetic PPAR-gamma agonists, and fibrates, which are PPAR-alpha agonists, to induce PPAR transcriptional activity, as well as to lower glucose and triacylglycerol levels in db/db mice. We further found that BVC occupies a novel alternative binding site in addition to the canonical site of synthetic agonists of PPAR, and that the synthetic PPAR-gamma agonist rosiglitazone can block BVC binding to this canonical site but not to the alternative site. Conclusions/interpretation This is the first report of a synergistic glucose-and lipid-lowering effect of BVC and synthetic agonists induced by unique binding with PPAR-gamma or -alpha. This combination may improve the efficacy and decrease the toxicity of marketed drugs for use as adjunctive therapy to treat the metabolic syndrome. |
| WOS关键词 | PROLIFERATOR-ACTIVATED RECEPTORS ; PEROXISOME PROLIFERATOR ; INSULIN-RESISTANCE ; NUCLEAR RECEPTOR ; DELTA ; BEZAFIBRATE ; LIGAND ; PHOSPHORYLATION ; ROSIGLITAZONE ; DYSLIPIDEMIA |
| 资助项目 | National Natural Science Fund[81172951] ; Eastern Scholar Tracking Program of Shanghai Municipal Education Commission[2012-90] ; 'Xinlin' Scholars and Shanghai E-Research Institute of Bioactive Constituent in TCM Plan[00000000] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| 出版者 | SPRINGER |
| WOS记录号 | WOS:000378048500026 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276017]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Guo, Fujiang; Huang, Cheng; Li, Yiming |
| 作者单位 | 1.Shanghai Univ Tradit Chinese Med, Sch Pharm, Dept TCM Chem, 1200 Cailun Rd, Shanghai 201203, Peoples R China; 2.Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, Houston, TX 77030 USA 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Membrane Res, Shanghai 200031, Peoples R China; 4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Peoples R China; 5.Shanghai Univ Tradit Chinese Med, Lab Drug Discovery, Sch Pharm, 1200 Cailun Rd, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Feng, Li,Luo, Huan,Xu, Zhijian,et al. Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-gamma and PPAR-alpha agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice[J]. DIABETOLOGIA,2016,59(6):1276-1286. |
| APA | Feng, Li.,Luo, Huan.,Xu, Zhijian.,Yang, Zhuo.,Du, Guoxin.,...&Li, Yiming.(2016).Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-gamma and PPAR-alpha agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice.DIABETOLOGIA,59(6),1276-1286. |
| MLA | Feng, Li,et al."Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-gamma and PPAR-alpha agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice".DIABETOLOGIA 59.6(2016):1276-1286. |
入库方式： OAI收割
来源：上海药物研究所
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