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阿利松 A 通过 AMPK/ACC/SREBP-1c 通路减轻高脂饮食诱导的肥胖和代谢紊乱。

Alisol A attenuates high-fat-diet-induced obesity and metabolic disorders via the AMPK/ACC/SREBP-1c pathway.

机构信息

Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering Research Center, Shanghai, China.

出版信息

J Cell Mol Med. 2019 Aug;23(8):5108-5118. doi: 10.1111/jcmm.14380. Epub 2019 May 29.

Abstract

Obesity and its associated metabolic disorders such as diabetes, hepatic steatosis and chronic heart diseases are affecting billions of individuals. However there is no satisfactory drug to treat such diseases. In this study, we found that alisol A, a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis, could significantly attenuate high-fat-diet-induced obesity. Our biochemical detection demonstrated that alisol A remarkably decreased lipid levels, alleviated glucose metabolism disorders and insulin resistance in high-fat-diet-induced obese mice. We also found that alisol A reduced hepatic steatosis and improved liver function in the obese mice model.In addition, protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP-1c pathway. As suggested by the molecular docking study, such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK.Therefore, we believe that Alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.

摘要

肥胖及其相关代谢紊乱,如糖尿病、肝脂肪变性和慢性心脏病,正在影响着数十亿人。然而,目前还没有令人满意的药物来治疗这些疾病。在这项研究中,我们发现,泽泻醇 A 是一种从中药泽泻中分离得到的主要活性三萜,可显著减轻高脂饮食诱导的肥胖。我们的生化检测表明,泽泻醇 A 可显著降低高脂饮食诱导肥胖小鼠的脂质水平,改善葡萄糖代谢紊乱和胰岛素抵抗。我们还发现,泽泻醇 A 可减少肥胖小鼠模型中的肝脂肪变性并改善肝功能。此外,蛋白表达研究表明,泽泻醇 A 对 AMPK/ACC/SREBP-1c 通路具有积极作用。分子对接研究表明,泽泻醇 A 的这种生物活性可能源于其对 AMPK 催化区域的选择性结合。因此,我们认为泽泻醇 A 可作为治疗肥胖及其相关代谢疾病的一种有前途的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b1a/6653754/8ca3d2754f04/JCMM-23-5108-g001.jpg

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