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葡萄球菌茎中的α-葡萄糖苷酶和细菌β-葡萄糖醛酸酶抑制剂

α-Glucosidase and Bacterial β-Glucuronidase Inhibitors from the Stems of Staph.

作者信息

Rao Guiwei, Yu Hangfei, Zhang Manlai, Cheng Yuchen, Ran Kun, Wang Jianwei, Wei Bin, Li Min, Shan Weiguang, Zhan Zhajun, Ying Youmin

机构信息

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.

Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou 310015, China.

出版信息

Pharmaceuticals (Basel). 2022 Mar 9;15(3):329. doi: 10.3390/ph15030329.

Abstract

α-Glucosidase (AGS) is a therapeutic target for Type 2 diabetes mellitus (T2DM) that tends to complicate with other diseases. Some medications for the treatment of T2DM complications have the risk of inducing severe adverse reactions such as diarrhea via the metabolism of intestinal bacterial β-glucuronidase (BGUS). The development of new AGS and/or BGUS inhibitors may improve the therapeutic effects of T2DM and its complications. The present work focused on the isolation and characterization of AGS and/or BGUS inhibitors from the medicinal plant . A total of eight compounds were isolated and identified. Sphaerandralide A () was obtained as a previously undescribed triterpenoid, which may have chemotaxonomy significance in the authentication of the genus and . 2'-acetyl-4',4-dimethoxybiphenyl-2-carbaldehyde () was obtained from a plant source for the first time, while compounds - were isolated from for the first time. In the in vitro assay, compounds - showed potent to moderate activity against AGS. Interestingly, compound also exhibited significant BGUS inhibitory activity, demonstrating the potential of being developed as a bifunctional inhibitor that may find application in the therapy of T2DM and/or the diarrhea induced by medications for the treatment of T2DM complications.

摘要

α-葡萄糖苷酶(AGS)是2型糖尿病(T2DM)的一个治疗靶点,T2DM往往会并发其他疾病。一些用于治疗T2DM并发症的药物有通过肠道细菌β-葡萄糖醛酸酶(BGUS)代谢引发严重不良反应如腹泻的风险。新型AGS和/或BGUS抑制剂的开发可能会改善T2DM及其并发症的治疗效果。目前的工作聚焦于从药用植物中分离和鉴定AGS和/或BGUS抑制剂。总共分离并鉴定出了8种化合物。球花内酯A()是一种之前未描述过的三萜类化合物,它可能在属和属的鉴定中有化学分类学意义。2'-乙酰基-4',4-二甲氧基联苯-2-甲醛()首次从植物来源获得,而化合物-首次从分离得到。在体外试验中,化合物-对AGS表现出强效至中度活性。有趣的是,化合物还表现出显著的BGUS抑制活性,表明其有开发成双功能抑制剂的潜力,这种抑制剂可能会用于T2DM治疗和/或治疗T2DM并发症药物引起的腹泻。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f56/8954508/d814b81fef88/pharmaceuticals-15-00329-g001.jpg

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