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Study Of The Hypoglycemic Active Compounds From Thunbergia And Metabolomic Data Analysis Method

Posted on:2013-02-04Degree:MasterType:Thesis
Country:ChinaCandidate:J X SongFull Text:PDF
GTID:2214330362459745Subject:Pharmaceutical Engineering
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Diabetes is a group of common endocrine and metabolic syndrome which would cause ketoacidosis,nonketotic hyperosmolar coma,diabetic nephropathy,diabetic neuropathy and other complication, seriously affecting human health and reducing quality of life. Currently, there are at least 171 million people suffering from diabetes and that would double to 366 million people in 2030, the number of diabetic patients in China has reached to 40 million; the World Health Organization serve diabetes as one of the three most difficult diseases. Chinese Medicine has accumulated experience for thousands of years in treating XiaoKeZheng what was called diabetes in modern medicine. In recent years, lots of research on treating diabetes with component in natural medicine and TCM has showed amazing results. This subject systematically researched the basic chemicals and filtered the hypoglycemic active ingredients in Thunbergia:a tropical plant that can treat diabetes in the folk.Thunbergia belong to the Acanthaceae Thunbergia genus, it is reported to contain iridoid, flavonoids, phenols and other ingredients, and the pharmacological activity studies shows Thunbergia is activeties in hypoglycemic, hepatoprotective and anti-aflatoxin. This subject filtered aldose reductase activity of Thunbergia ethanol total extract, the results shows Thunbergia can significantly inhibit aldose reductase with Dose- dependent relationship. In order to find the active ingredients, we devided ethanol total extract into two parts, ethyl acetate and n-butanol, accord- ing to polarity, and tracked the Aldose reductase activity respectively. As a result, the ethyl acetate part showed good Aldose reductase inhibitory activity with obvious Dose-dependent relationship; on the contrary, the n- butanol part with no inhibition in the same dose range. On the basis of previous study, we systematically separated the chemical composition of the ethyl acetate part and tested the hypoglycemic activity of the mono- mers. Nine compounds have been separated from the ethyl acetate part, the structure of these compounds were identified by the IR,EI-MS,1H-NMR,13C-NMR,2D-NMR etc. The nine compounds are (1) 8-(- Glucopyranosyloxy)-4,3-dihydro-5,4-dihydroxy-2-(3-methyl-2-butenyl) naphtha[2,3-b]oxirene-1(2H)-one,(2) 4,3-Dihydro-8,5,4-trihydroxy-2- (3-methyl-2-butenyl)naphtha[2,3-b]oxir-en-1(2H)-one,(3) Thunbergin A,(4) Thunbergin B,(5) Galangin,(6) Quercetin,(7) Luteolin,(8) 5,6,3 ', 4'-hydroxy -3,7 - dimethoxy flavone and lupine alcohol. Among them, compound 3 and 4 are new compounds, compound 1 and 2 are firstly separated in this species. Further more , compound 3 showed good inhibit aldose reductase activity.Another part of this paper is the methodological research on metabolic data pretreatment. Metabolomics mainly determine the metabolomic information of all the small-molecule metabolites(molecular weight less than 1000) in biological fluids(such as blood,urine),cell extracts and tissue or tissue extract solution, it reveal the integrated difference of series of associated biomarkers that would completely analysis the impact of disease on biological systems. There are many research tools used in metabolomics, including chromatography-mass spectrometry, such as GC-MS,LC-MS,CE-MS,NMR and NMR-MS etc. Data analysis method include one-dimensional(Hypothesis testing and analysis) and multi-dimensilnal (principal compound analusis, nonlinear mapping, partial least squares regression, and neural networks). As metabolic data pretreatment do not attach importance to adjust the variable distribution in the process of pretreatment, this subject tried to adjust the distribution of the liver cancer metabolic data with Box-Cox transformation, and esta-blished PCA,PLS-DA,OPLS-DA model with the transformed data. Our result showed that the application of Box-Cox pretreament can significantly improve the explanation rate and predictive ability of the model, this provided a good method in disease diagnosis and subtype classification.
Keywords/Search Tags:Thunbergia, Chemical composition, Aldose reductase, Box-Cox, PCA, PLS-DA and OPLS-DA
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