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Islet protection and amelioration of type 2 diabetes mellitus by treatment with quercetin from the flowers of Edgeworthia gardneri

Authors :
Zhuang,Manjiao
Qiu,Honghong
Li,Ping
Hu,Lihua
Wang,Yayu
Rao,Lei
Source :
Drug Design, Development and Therapy.
Publication Year :
2018
Publisher :
Dove Press, 2018.

Abstract

Manjiao Zhuang,1 Honghong Qiu,2 Ping Li,2 Lihua Hu,2 Yayu Wang,3 Lei Rao2 1Department of Pharmacy, Sichuan University, Chengdu, People’s Republic of China; 2Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, China; 3Department of Cell Biology, Institute of Biological Medicine, Jinan University, Guangzhou, People’s Republic of China Background and purpose: The traditional Chinese medicine – the flower of Edgeworthia gardneri – is reported as an effective therapeutic for type 2 diabetes mellitus (T2DM). Nevertheless, most constituents of the flowers of E. gardneri have not yet been studied. This study was conducted to investigate the effect of quercetin extracted from the flowers of E. gardneri on islet protection and amelioration in T2DM and explore its mechanism. Method: Quercetin was extracted from the flowers of E. gardneri and verified by high-performance liquid chromatography. Quercetin or crude extract’s effect on insulin secretion was investigated. ERK1/2 and phospho-ERK1/2 were detected by Western blot analysis, and fluo-3 AM was used to detect intracellular Ca2+. The anti-apoptosis effect of quercetin or crude extract on MIN-6 cells was investigated by thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometry analysis. Activation of caspases and expression of Bcl-2 and BAX were tested by Western blot analysis. In addition, the mitochondrial membrane potential was determined by JC-1 probe. Moreover, in vivo activity was also tested in db/db mice. Results: A quercetin level of >10 μmol/L could induce insulin secretion. Intracellular Ca2+ and ERK1/2 were involved in the signaling pathway of quercetin-induced insulin secretion. We also observed that quercetin could inhibit palmitic acid-induced cell apoptosis via suppressing the activation of caspase-3, -9, -12; increasing the ratio of Bcl-2/BAX and reversing the impaired mitochondrial membrane potential. Crude extract’s effect on insulin secretion was similar to that of pure extracted quercetin, while it possessed higher anti-apoptosis activity. Additionally, intraperitoneal glucose tolerance, plasma insulin level, hepatic triglyceride, hepatic glycogen and the pathological histology of both pancreatic islet and liver in db/db mice were significantly improved by the administration of the extracted quercetin. Conclusion: Our study indicated that quercetin extracted from the flowers of E. gardneri exerted excellent properties in islet protection and amelioration. Keywords: quercetin, Edgeworthia gardneri, insulin secretion, anti-apoptosis, type 2 diabetes mellitus

Details

Language :
English
ISSN :
11778881
Database :
OpenAIRE
Journal :
Drug Design, Development and Therapy
Accession number :
edsair.dovemedicalp..f45605dd01a1df82f6303c539f2c5d80