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Study On The Medicinal Substances And Mechanism Of Action Of Gynura Procumbens (Lour.) Merr. On The Improvement Of Type 2 Diabetes Mellitus Based On Liquid Chromatography-Mass Spectrometry And Metabolomics

Posted on:2020-05-20Degree:MasterType:Thesis
Country:ChinaCandidate:M LiuFull Text:PDF
GTID:2404330590997445Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Type ? diabetes is a chronic metabolic disease that usually has clinical symptoms such as chronic hyperglycemia and insufficient insulin secretion.Uncontrolled diabetes can lead to long-term health complications,including heart disease,stroke,blindness and kidney failure.According to the latest data of the International Diabetes Federation,there are 425 million people with diabetes in the world aged 20-79,of which type ? diabetes accounts for 90-95%.It can be seen that type 2 diabetes seriously affects human health and quality of life.At present,in addition to oral hypoglycemic agents,insulin injection is also the main strategy for the treatment of diabetes.In clinical practice,although drugs such as sulfonylureas and biguanides can control blood glucose levels in patients,these drugs have adverse toxic side effects on health and have no protective effect on islet B cells.Therefore,more and more people are keen to use natural products to prevent and treat type 2 diabetes.Gynura procumbens is a perennial herbaceous food homologous plant.It has been reported in the literature to have a good hypoglycemic effect,but so far,its pharmacodynamic components and mechanism of action are still unclear.Based on this,the paper carries out the following research:1.Study on the chemical constituents of Gynura procumbens based on UHPLC-Q-TOF-MS/MSAt present,there is only a small amount of research on the chemical constituents of Gynura procumbens.The literature mainly uses the traditional method of separation and extraction of traditional Chinese medicine chemical components.This method is usually time-consuming and labor-intensive,especially some trace chemical components are easily ignored.It is not conducive to the comprehensive discovery of the chemical composition of the Gynura procumbens.UHPLC-QTOF-MS/MS technology has the characteristics of high efficiency,rapidity,high resolution and high sensitivity.In recent years,it has been widely used in the study of chemical constituents of Chinese medicine and its metabolism in vivo.Therefore,on the basis of the separation of chemical components in the early stage,UHPLC-QTOF-MS/MS technology was used to study the chemical constituents of Gynura procumbens Through reference control,literature data,online search tools,combined with characteristic ion and neutral loss scanning strategy,81 combinations were identified from Gynura procumbens,including 17 kinds of flavonoids and 24 kinds of phenylpropanoids.There are 13 organic acids and 27 other compounds.This study laid the foundation for the basic research of the pharmacodynamics of Gynura procumbens.2.Evaluation of the effect of Gynura procumbens in treatment of type 2 diabetes mellitusThe db/db model mouse is a spontaneous type 2 diabetic mouse with clinical features of type 2 diabetes such as hyperinsulinemia,hyperlipidemia,and hyperglycemia.It is the best model for studying type 2 diabetes.In order to further study the effect of Pingyao Sanqi on the improvement of type ? diabetes mellitus,this experiment used db/db model to carry out the general behavior,blood glucose,insulin,blood lipids and pathology of mouse pancreas in the mice.The effect of comprehensive evaluation of the role of Pingyao Sanqi in the treatment of diabetes.The experimental results show that Gynura procumbens has the effect of improving type ? diabetes.This experiment laid the foundation for the follow-up study on the mechanism of action of Gynura procumbens in improving diabetes.3.study of Serum Metabolomics in Type 2 Diabetes Mellitus treatment by Gynura procumbensMetabolomics is generally a means of disease diagnosis and drug analysis and has been considered a promising and reliable new diagnostic method.The LC-MSbased metabolomics approach provides rapid access to comprehensive information on endogenous metabolites in biological samples.Based on the improvement of diabetes efficacy in db/db mice,the experiment used UHPLC-Q-TOF-MS/MS and metabolomics techniques to study the serum of diabetic mice.Firstly,a serum sample analysis method was established,and the method stability of the analysis method was investigated using QC samples.A total of 50 potential biomarkers were identified by data analysis.Metabolic pathway enrichment topological analysis revealed glycerol phosphate metabolism,retinol metabolism,glycosylphosphatidylinositol(GPI)-anchored biosynthesis,pyrimidine metabolism,tryptophan metabolism,arginine and proline metabolism,glutathione metabolism,sphingolipid metabolism are closely related to serum metabolism of type 2 diabetes in db/db mice.It was found that Gynura procumbens can regulate glycerol phosphate metabolism,retinol metabolism and glycosylphosphatidylinositol(GPI)-anchored biosynthesis by regulating phospholipids,sphingolipids and amino acids in mouse serum.To improve type 2 diabetes in db/db mice 4.study of Urine metabonomics in Type 2 Diabetes Mellitus treatment by Gynura procumbensIn metabolomics research,urine is non-invasive and more convenient,but it is often overlooked.Clinically,diabetic patients need to check urine routines frequently,and indicators of response from urine contribute to the diagnosis and treatment of the disease.Therefore,this experiment used metabolomics techniques to study the urine of diabetic model mice.A total of 21 potential biomarkers were found in the urinary metabolome analysis.The phenylalanine,tyrosine and tryptophan biosynthesis,tyrosine metabolism and glycerol phosphate metabolism were found with db/db through metabolic pathway enrichment topology.Mouse type 2 diabetes is closely related.The glycerol phosphate metabolic pathway is consistent with the pathway identified by serum metabolomics.It has been found that Gynura procumbens can improve diabetes by lowering the levels of tyrosine and glycerol phosphate ethanolamine to improve tyrosine and glycerol phosphate metabolism.
Keywords/Search Tags:Gynura procumbens, Chemical constituents, Type ? diabetes mellitus, Metabonomics, Biomarkers, Metabolic pathways
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