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Study On Metabonomics Of Total Flavonoids In Bupleurum Smithii Wolff Var. Parvifolium

Posted on:2013-11-17Degree:MasterType:Thesis
Country:ChinaCandidate:H L WuFull Text:PDF
GTID:2234330362471411Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
The total flavonoids with Bupleurum smithii Wolff var. parvifolium is mainlyexist in the part of its stems and leaves. Composition of the class has a distinct role inthe hepatoprotective, choleretic, jaundice. Shows a good prospects for clinicalapplication., but for the pathways and mechanisms is in vivo metabolic is not yetentirely clear.The core idea of metabonomics is research the overall effect ofexogenous substances on the organism, and take the whole of the molecules ofbiological substances as body is an object, research the overall role of themetabonomics for drugs on the body. This idea is consistent with the overall conceptof the theory of traditional Chinese medicine treatment of diseases, so it’s a goodmethod for study the efficacy and mechanism of action of traditional Chinese medicine.This topic use the induced liver toxicity by ANIT, manufacturing Wistar rats werecholestatic hepatitis model,and pharmacodynamic study of the total flavonoids;Collection of animals serum and urine,and use UPLC-Q-TOF/MS technologycombined with multi-dimensional mode discriminant analysis method to analyze thechanges in their metabolic fingerprint. Carry out the study of metabonomics for totalflavonoids.The main findings are as follows:1. The total flavonoids have significant choleretic effect and can significantlyreduce the ALT, AST, TBIL, GGT and ALP (P<0.01) of cholestatic hepatitis inducedby ANIT;2. Serum metabonomics experiments found that: Compared with the normalrats, phospholipid metabolism, fatty acid metabolism, arachidonic acid metabolis-m,porphyrin metabolism, bile acid metabolism sphingolipid metabolism some amino acids and vitamin metabolism and other metabolic pathway changes in model group ratsserum. After the intervention of the total flavonoids, we found thatthe phospholipid metabolism,bile acid metabolism, porphyrin metabolism, arachi donic acid metabolism, fatty acid metabolism, cholesterol metabolism and othermetabolic pathways tendto balance.Prompt total flavonoids may be treatmentthecholestatic hepatitis from to the above channels.3. Urine metabonomics experiments found that: the hippuri acid, heptanoylcarnitine,5β-Cholestane-3α-7α-12α-23R-25-pentol, phytosphingosine,6-Keto-prostaglandinF1α,3-Sulfodeoxycholic acid, sphinganine, lysoPE(0:0/24:0), phenylacetylglycine and other endogenous substances in treatment group rat urine metabolitechanged significantly compared with model group.The total flavonoids can affectphospholipid metabolism, sphingolipid metabolism, fatty acid metabolism of arachidonic acid metabolism, bile acid metabolism, cholesterol metabolism and other metabolic pathways in cholestatic hepatitis model rats vivo.This project confirmed that the significant role in anti-cholestatic hepatitis of totalflavonoids. Study on the metabolic pathways and mechanismsthe use metabolomicsfor the first time, and revealed the role of the characteristics with total flavonoids ismulti-channel, multi-target. Provides a theoretical and experimental basis for a betterunderstanding of the efficacy value of Bupleurum smithii Wolff var. parvifolium. Atthe same time provide methods and ideas for the study of Chinese medicine angle frommetabonomics.
Keywords/Search Tags:Bupleurum smithii Wolff var. parvifolium, total flavonoids, metabonomics, cholestatic hepatitis, biomarkers
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