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Screening Activities Of Traditional Chinese Medicines For Treating Diabetes And Faeces Metabonomics Study Of Type 2 Diabetic Rats

Posted on:2017-04-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhouFull Text:PDF
GTID:2284330482495675Subject:Pharmaceutical
Abstract/Summary:PDF Full Text Request
Diabetes is a metabolic disease characterized by high blood glucose and caused by absolute or relative lack of insulin. Long-term high blood glucose condition in vivo would lead to the lesion of eye, kidney, heart and other tissues and organs, these lesions are known as diabetic complications. The pathogenesis and therapeutic mechanism of diabetes and diabetic complications are complicated and various.There are about two hundred kinds of traditional Chinese medicines for treating diabetes, and their treatment are multicomponent and multi-path, so their therapeutic mechanism are still unclear. In this study, the potential bioactivities of about 20 kinds of traditional Chinese medicines in treating diabates and diabetic complications are investigated in three aspects, respectively are the activity in inhibiting advanced glycation end products formation, the activity in inhibiting lipid peroxidation and the glucosidase inhibitory activity.In vitro experiment screened Lonicerae Japonicae Flos etc 8 traditional Chinese medicines which have rather strong activity in inhibiting advanced glycation end products formation, and Caryophylli Flos etc 9 medicines for strong activity in inhibiting lipid peroxidation, Sophorae Tonkinensis Radix Et Rhizoma 9 medicines for glucosidase inhibitory activity. According to component analysis, the traditional Chinese medicines which contains much flavonoid or phenols show stronger activity in inhibiting advanced glycation end products formation and lipid peroxidation. However, the effective components of glucosidase inhibitory activity are various.Based on experimental reasults and pertinent literatures, the study choosed geniposide, iridoids from Gardenlae Fructus, the extractive of Scutellarlae Radix and Gardenlae Fructus as reasearch objects, investigated the faeces metabonomics of type 2 diabetic rats. We established the model of type 2 diabetic by giving a gavage of fat emulsion and injecting STZ, after sectionalization, gavaged for 12 weeks and collected faeces termly. Then detect the faeces of control group, model group and T2 DM rats treating groups depended on UPLC-QTOF-MS. The LC/MS/MS data was imported to Mass Lynx V4.1 and Marker Lynx Application Manager for disposing peaks, then the detected compounds were analyzed by PCA and OPLS-DA with EZinfo 2.0 software. After that, the VIP scores which denote the content difference of metabolites in groups would be figure out by t-test based on PASW Statistics 18.0 software. According to Human Metabolome Database(HMDB) and other relevant biological database, we found out potential biomarkers and then matched the HPLC tandem mass spectrometry imformation with these biomarkers to confirm them. So we could analyze the changes of metabolic pathways reflected by potential biomarkers, illuminated these changes caused by diabetes and the mechanisms of each traditional Chinese medicine.The research results indicate that geniposide, iridoids from Gardenlae Fructus, the extractive of Scutellarlae Radix and Gardenlae Fructus all have a therapeutic effect to T2 DM rats. We analyzed and identified 36 potential biomarkers, according to this markers, we could see the changes of amino acid metabolic pathways, fatty acid synthesis pathways, sphingolipid metabolism pathways, bile acids and other metabolites. Geniposide, iridoids from Gardenlae Fructus, the extractive of Scutellarlae Radix and Gardenlae Fructus these three can adjust amino acid metabolic pathways, sphingolipid metabolism pathways and bile acids with different degrees, but they have little effect to fatty acid synthesis pathways.
Keywords/Search Tags:tiabetes, traditional Chinese medicines, bioactivity screening, metabolomics, LC-MS, biomarkers
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