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

Abstract

Background and purposeThe 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.MethodQuercetin 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.ResultsA 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.ConclusionOur study indicated that quercetin extracted from the flowers of E. gardneri exerted excellent properties in islet protection and amelioration.

Serum metabonomics analysis of quercetin against the toxicity induced by cadmium in rats

“…Quercetin is a natural flavonoid that is widely distributed in fruits and vegetables. [ 8 ] It has antioxidant, anti‐inflammatory, antitumor, and antimutation physiological functions. [ 9–12 ] Epidemiologic studies have suggested that increasing quercetin intake can reduce the risk of certain chronic diseases, such as cardiovascular disease, osteoporosis, and diabetes.…”

Quercetin promotes long noncoding RNA lncSHGL expression via estrogen receptor α to suppress type 2 diabetes mellitus in mice

“…These compounds have received much attention due to their structural diversity, richness, strong pharmacological activity, and safety [38]. Numerous studies have reported the biological effects of quercetin, and its potential benefits as an anti-cancer, anti-oxidative, and anti-inflammatory agent, especially in the treatment of type 2 diabetes mellitus [39][40][41][42]. Quercetin can improve the symptoms and eliminate the complications of diabetes [38,43,44].…”

Urolithin C increases glucose‐induced ERK activation which contributes to insulin secretion

“…We and others reported that the polyphenol quercetin enhanced the insulin secreting activity of pancreatic b-cells and protected this key function from environmental insults which is crucial for appropriate control of glucose homeostasis [7,16,17,22,23]. Mechanistically, quercetin facilitated depolarization-induced L-type Ca 2+ currents and increased intracellular Ca 2+ concentration which is essential to trigger exocytosis [24].…”

“…Importantly, quercetin also enhanced glucose-mediated ERK1/2 activation which contributes to its insulin secreting action. Indeed, inhibition of MAPK kinases (MAPKK) proteins, the upstream activators of ERK1/2, decreased the stimulatory effect of quercetin on glucose-induced insulin secretion [16,22]. Besides polyphenols, we recently reported that a few of their metabolites also exert pharmacological action in pancreatic b-cells.…”