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Anti-diabetic Activity And Mechanism Of Flavonoids Components From Chrysanthemum Morifolium

Posted on:2020-03-09Degree:MasterType:Thesis
Country:ChinaCandidate:M Z ChenFull Text:PDF
GTID:2404330602965740Subject:Medicinal Chemistry
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Diabetes mellitus,a kind of endocrine disease affected by genetic and environmental,harm human health seriously.Diabetes has become a serious problem in many countries.Inhibitions of a-glucosidase and PTP-1B are studied as methods for controlling blood sugar levels.a-Glucosidase catalyzes the final step of carbohydrate digestion and releases glucose from oligosaccharides,and PTP-1B is a key negative regulator protein in insulin signaling pathways.a-Glucosidase inhibitors slow the release of glucose from oligosaccharides,PTP-1B inhibitors can increase the secretion of insulin and decrease postprandial blood glucose levels.The dual inhibitors were especially suitable for Asian whose main food sources were carbohydrates.Preliminary laboratory studies had found that flavonoids have a variety of pharmacological activities,such as:anti-cancer,anti-malaria,anti-inflammatory,anti-oxidation,anti-tuberculosis,anti-bacterial,hypoglycemic and other activities.This project intended to study the anti-diabetes activity of flavonoids from chrysanthemum.Firstly,the components of flavonoids were extracted from chrysanthemum morifolium and identified by LC-MS.Then,the enzyme inhibition activity of these compounds was evaluated,including a-glucosidase,dipeptidyl peptidase-4 and PTP-1B.HepG2 cells were used for glucose consumption-promoting evaluation,and insulin-secretion activity was evaluated in INS-1 cells.Finally,anti-diabetic activity was evaluated in type 2 diabetic mice.The results showed that the flavonoids in chrysanthemum had the dual inhibitory activity of a-glucosidase and PTP-IB,and the activity of glucose consumption-promoting in HepG2 cells.Diosmetin 7-glucoside and diosmin can also promote insulin secretion in INS-1 cells.Western blot indicated that the flavonoids also increased the expression of pIRS-1,pAkt and pGSK3p and inhibited the expression of PTP-1B.Through the analysis of hypoglycemic activity in mice,both the high-dose and low-dose groups of apigenin and diosmin can significantly reduced postprandial blood glucose levels,improved the oral glucose and maltose tolerance of mice,and decreased the content of glycerol and cholesterol.In addition,it can also relieve histological morphology such as liver cell boundary ambiguity,cell arrangement disorder,water like degeneration of cytoplasmic vacuolation,and liver lobule structure disappearance.Therefore,the flavonoids in chrysanthemum morifolium had dual inhibitory activity on a-glucosidase and PTP-1B,increased glucose consumption,promoted insulin secretion,and reduced hyperglycemia and hyperlipidemia in diabetic mice.It's potential to become a functional food and candidate drug for the treatment of type 2 diabetes.
Keywords/Search Tags:?-glucosidase, PTP-1B, anti-diabetes, flavonoids
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