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Luteolin Protects Pancreatic beta Cells against Apoptosis through Regulation of Autophagy and ROS Clearance

文献类型：期刊论文

作者Han, Ming1,2; Lu, Yuting2; Tao, Yunhua2; Zhang, Xinwen2; Dai, Chengqiu3,4; Zhang, Bingqian2,3; Xu, Honghong2; Li, Jingya1,2,3,4
刊名PHARMACEUTICALS
出版日期2023-07-01
卷号16期号:7页码:17
关键词luteolin type 2 diabetes beta cell autophagy reactive oxygen species
DOI10.3390/ph16070975
通讯作者Lu, Yuting(ytlu@simm.ac.cn) ; Li, Jingya(jyli@simm.ac.cn)
英文摘要Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (beta) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved in regulating beta cell survival. Since natural products have multiple targets and often are multifunctional, making them promising compounds for the treatment of diabetes, we identified Drak2 inhibitors from a natural product library. Among the identified products, luteolin, a flavonoid, was found to be the most effective compound. In vitro, luteolin effectively alleviated palmitate (PA)-induced apoptosis of beta cells and PA-induced impairment of primary islet function. In vivo, luteolin showed a tendency to lower blood glucose levels. It also alleviated STZ-induced apoptosis of beta cells and metabolic disruption in mice. This function of luteolin partially relied on Drak2 inhibition. Furthermore, luteolin was also found to effectively relieve oxidative stress and promote autophagy in beta cells, possibly improving beta cell function and slowing the progression of diabetes. In conclusion, our findings show the promising effect of Drak2 inhibitors in relieving diabetes and offer a potential therapeutic target for the protection of beta cells. We also reveal some of the underlying mechanisms of luteolin's cytoprotective function.
WOS关键词DAP-KINASE ; SERINE/THREONINE KINASE ; OXIDATIVE STRESS ; GLUCOSE TOXICITY ; FATTY-ACIDS ; BECLIN 1 ; DRAK2 ; PHOSPHORYLATION ; OVEREXPRESSION ; INHIBITORS
资助项目National Natural Science Foundation of China[92057116] ; National Natural Science Foundation of China[81673493] ; National Natural Science Foundation of China[82200885] ; National Science and Technology Major Project[2018ZX09711002-004/018] ; Shanghai Municipal Science and Technology Committee of Shanghai outstanding academic leaders plan[22XD1400600]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者MDPI
WOS记录号WOS:001037487800001
源URL[http://119.78.100.183/handle/2S10ELR8/306869]  
专题新药研究国家重点实验室
通讯作者Lu, Yuting; Li, Jingya
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Han, Ming,Lu, Yuting,Tao, Yunhua,et al. Luteolin Protects Pancreatic beta Cells against Apoptosis through Regulation of Autophagy and ROS Clearance[J]. PHARMACEUTICALS,2023,16(7):17.
APA Han, Ming.,Lu, Yuting.,Tao, Yunhua.,Zhang, Xinwen.,Dai, Chengqiu.,...&Li, Jingya.(2023).Luteolin Protects Pancreatic beta Cells against Apoptosis through Regulation of Autophagy and ROS Clearance.PHARMACEUTICALS,16(7),17.
MLA Han, Ming,et al."Luteolin Protects Pancreatic beta Cells against Apoptosis through Regulation of Autophagy and ROS Clearance".PHARMACEUTICALS 16.7(2023):17.

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来源：上海药物研究所

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