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Study On The Effect Mechanism Of Fermented Citrus Medica Extract On The Improvement Of Disordered Glycolipid Metabolic Mice

Posted on:2022-02-01Degree:MasterType:Thesis
Country:ChinaCandidate:L WangFull Text:PDF
GTID:2504306554959809Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Glycolipid metabolic diseases are a class of diseases characterized by dysregulation of glycolipid metabolism,including non-alcoholic fatty liver disease,type 2 diabetes mellitus,atherosclerosis,etc.With the development of society,people gradually develop the habit of consuming high-calorie food and sedentary life,and glycolipid metabolic diseases have become one of the main chronic diseases in China.Because the pathogenesis of glycolipid metabolic diseases is very complex and treatment methods are scarce.Therefore,the development of related foods,drugs and health care products is of great significance for the treatment of glycolipid metabolic diseases.Flavonoids,phenolic acids and other compounds contained in Citrus medica are shown to regulate glucose and lipid metabolism.This topic will be Chinese traditional medicine Citrus medica and modern fermentation technology,the combination of Chinese traditional medicine preparation for the fermentation with higher content of active ingredients,by investigating the in vitro antioxidant activity of the fermentation Citrus medica explore its potential regulate glucolipid metabolism,and then establish the glucolipid metabolic disorder induced by high-fat diet animal model,evaluation of therapeutic effects of Citrus medica regulate glucolipid metabolism of fermentation.Finally,the possible mechanism of action was explored through network pharmacology,molecular simulation and mechanism studies.Through single factor screening method,the fermentation strains,temperature and time were investigated,to explore the best preparation technology of the fermentation.The results showed that under anaerobic conditions,the best fermentation strain was the mixed bacteria(Enterococcus faecium: Lactobacillus plantata=1:1),the best fermentation temperature was 37℃,the best fermentation time was 15 days.The results of the content determination of active components showed that the content of total flavonoids,total phenolic acid,total amino acid and total sugar increased by 68.20%,59.57%,59.26% and 27.24% respectively after the optimized fermentation.In vitro antioxidant experiments showed that compared with the extract,the scavenging rate of DPPH free radical,OH free radical,superoxide anion free radical and ABTS free radical were increased by 16.00 %,46.01 %,21.93 % and 34.09 % respectively.In conclusion,the fermented extract contained higher active components,had better antioxidant activity in vitro,and had the potential to regulate glucose and lipid metabolism disorders.The pharmacodynamics effects of fermented Citrus medica extract were investigated by establishing a mouse model with disordered glucose and lipid metabolism.In vivo animal experiments showed that the Citrus medica extract and fermentation Citrus medica extract does not affect food intake in mice,both can slow the body weight of mice growth trend,reduce the mice serum TC,TG and LDL-C level,improve the level of serum HDLC,reduces the degree of the liver and body lipid accumulation,reduce the content of serum insulin and insulin resistance,The levels of ALT,AST and MDA in liver were decreased,and the levels of SOD,CAT and GSH-Px in liver were increased.In addition,compared with Citrus medica extract,fermented Citrus medica extract could better regulate serum insulin,insulin resistance and liver oxidative stress.In conclusion,fermented Citrus medica extract can better regulate glucose and lipid metabolism disorders,especially has obvious advantages in alleviating oxidative stress and insulin resistance.Based on previous pharmacodynamics results and through network pharmacology,molecular docking experiments and mechanism studies,the possible mechanism of the fermented Citrus medica extract regulating glucose and lipid metabolism was explored.The network pharmacological exploration of glycolipid metabolic diseases and the hand of the hand has obtained 9 main pharmacodynamic components,29 core targets and 107 related pathways.The main pharmacodynamic components include Bergamottin,Diosmetin,Diosmin,etc.,and the core targets include TNF,NOS2,PPAR-γ,PI3 K,etc.The related pathways include insulin resistance,AGE-RAGE,PI3K-Akt,IL-17,tumor necrosis factor,etc.Animal experiments showed that compared with Citrus medica extract,fermented Citrus medica extract could better reduce the m RNA and protein levels of IL-6 and TNF-α in liver.In conclusion,fermented Citrus medica can reduce oxidative stress in the liver,possibly by mediating JNK/SAPK and PI3 K pathways to improve insulin resistance,and thus play a role in regulating glucose and lipid metabolism.
Keywords/Search Tags:Fermented Citrus medica, Glycolipid metabolic disease, Oxidative stress, Insulin resistance, Network pharmacology
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