仁济医院团队:丁内酯-I或能改善2型糖尿病
  • 体外筛选11种丁烯内酯衍生物的α-葡萄糖苷酶及TNF-α抑制活性,发现丁内酯-I(A6)是有效的α-葡萄糖苷酶抑制剂;
  • A6可降低2型糖尿病(T2D)小鼠血糖,减轻体重,改善葡萄糖耐量和胰岛素抵抗,增加短链脂肪酸(SCFA)水平,激活SCFA诱导的胰高血糖素样肽1和胰岛素增敏受体PPARγ的表达,增强肠粘膜屏障功能和减轻内毒素血症;
  • A6潜在的作用原理为肠道菌群调控,且具有稳定性和安全性,是极具前景的T2D的候选药物。
主编推荐语
潇洒小姐陈
上海交通大学医学院附属仁济医院团队,从真菌土曲霉(Aspergillus terreus)中分理出11种丁烯内酯,体外筛选后得出了一种2型糖尿病候选药物--丁内酯-I(A6),然后进行了体外的毒性药物活性等检测,以及动物检测(如血糖、肠容物代谢物及菌群成分)最后得出丁内酯-I或可作为T2D的候选药物。有兴趣的读者可以关注!
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片
FASEB Journal [IF:4.966]

Butyrolactone-I, an efficient α-glucosidase inhibitor, improves type 2 diabetes with potent TNF-α-lowering properties through modulating gut microbiota in db/db mice

一种有效的α-葡萄糖苷酶抑制剂--丁内酯-I通过调节db/db小鼠的肠道微生物,改善2型糖尿病并显著降低TNF-α。

10.1096/fj.201901061R

2019-08-26, Article

Abstract & Authors:展开

Abstract:收起
The aim of this study was to evaluate the effects of butyrolactone-I (A6) on type 2 diabetes (T2D) in db/db mice because A6 was found to inhibit α-glucosidase activities and TNF-α release, which were associated with improving T2D. Male db/db mice were divided into 6 groups and given an equivalent volume of olive oil, acarbose, or different doses of A6 for 4 wk ( = 8/group). In this study, 11 butenolide derivatives were screened for their α-glucosidase and TNF-α suppressive activity . A6, an efficient α-glucosidase inhibitor, exerts hypoglycemic and multiple activities in reducing weight, improving glucose tolerance and insulin resistance, increasing short-chain fatty acid (SCFA) levels, activating SCFA-induced increases in glucagon-like peptide 1 and peroxisome proliferator-activated receptor-γ expression, enhancing intestinal mucosal barrier function and mitigating endoxemia in db/db mice. These effects may result from mediation of gut microbiota by A6. Meanwhile, A6, with potent TNF-α-lowering properties, was demonstrated to have multiple salutary effects with excellent structural stability and long-term safety . A6, an effective α-glucosidase inhibitor with high security and stability, exerted potent antidiabetic effects . Furthermore, the modulation of gut microbiota of A6 was demonstrated to be one of the mechanisms contributing to anti-inflammation properties and improving endoxemia. Our work confirms that the compound A6 is a prospective drug candidate for T2D.-Wu, W., Liu, L., Zhu, H., Sun, Y., Wu, Y., Liao, H., Gui, Y., Li, L., Liu, L., Sun, F., Lin, H. Butyrolactone-I, an efficient α-glucosidase inhibitor, improves type 2 diabetes with potent TNF-α-lowering properties through modulating gut microbiota in db/db mice.

First Authors:
Wei Wu,Liyun Liu,Hongrui Zhu

Correspondence Authors:
Fan Sun,Houwen Lin

All Authors:
Wei Wu,Liyun Liu,Hongrui Zhu,Yating Sun,Ying Wu,Hongze Liao,Yuhan Gui,Lei Li,Lei Liu,Fan Sun,Houwen Lin

评论