PMID- 29720871 OWN - NLM STAT- MEDLINE DCOM- 20181011 LR - 20220317 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 12 DP - 2018 TI - Islet protection and amelioration of type 2 diabetes mellitus by treatment with quercetin from the flowers of Edgeworthia gardneri. PG - 955-966 LID - 10.2147/DDDT.S153898 [doi] AB - 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 Ca(2+). 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 mumol/L could induce insulin secretion. Intracellular Ca(2+) 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. FAU - Zhuang, Manjiao AU - Zhuang M AD - Department of Pharmacy, Sichuan University, Chengdu, People's Republic of China. FAU - Qiu, Honghong AU - Qiu H AD - Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, China. FAU - Li, Ping AU - Li P AD - Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, China. FAU - Hu, Lihua AU - Hu L AD - Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, China. FAU - Wang, Yayu AU - Wang Y AD - Department of Cell Biology, Institute of Biological Medicine, Jinan University, Guangzhou, People's Republic of China. FAU - Rao, Lei AU - Rao L AD - Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, China. LA - eng PT - Journal Article DEP - 20180423 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Antioxidants) RN - 0 (Insulin) RN - 2V16EO95H1 (Palmitic Acid) RN - 9IKM0I5T1E (Quercetin) SB - IM MH - Animals MH - Antioxidants/administration & dosage/isolation & purification/*pharmacology MH - Apoptosis/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Diabetes Mellitus, Experimental/*drug therapy/metabolism MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Flowers/*chemistry MH - Humans MH - Insulin/blood/*metabolism MH - Medicine, Chinese Traditional MH - Membrane Potential, Mitochondrial/drug effects MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Palmitic Acid/antagonists & inhibitors/pharmacology MH - Quercetin/administration & dosage/isolation & purification/*pharmacology MH - Thymelaeaceae/*chemistry PMC - PMC5918626 OTO - NOTNLM OT - Edgeworthia gardneri OT - anti-apoptosis OT - insulin secretion OT - quercetin OT - type 2 diabetes mellitus COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/05/04 06:00 MHDA- 2018/10/12 06:00 PMCR- 2018/04/23 CRDT- 2018/05/04 06:00 PHST- 2018/05/04 06:00 [entrez] PHST- 2018/05/04 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] PHST- 2018/04/23 00:00 [pmc-release] AID - dddt-12-955 [pii] AID - 10.2147/DDDT.S153898 [doi] PST - epublish SO - Drug Des Devel Ther. 2018 Apr 23;12:955-966. doi: 10.2147/DDDT.S153898. eCollection 2018.