Study On Spectrum-effect Relationship And Metabolism Of Anti-gastric Ulcer Effects In Radix Astragali

The quality evaluation of Traditional Chinese Medicine (TCM) has always been the nodus and emphasis both in the research and application. However, most research on quality evaluation is focusing on the chemical constituents, but it cannot reflect the curative effect of TCM. A more reasonable quality evaluation system should reflect the pharmacological action instead of simple chemical constituents’ qualitative and quantitative analysis. The thesis studied Radix Astragali as an example. The anti-gastric ulcer activity (AUA) of Radix Astragali from five different polar parts was studied in vivo. Ten batches of samples from different geographic regions were used to create the fingerprints of the High-performance liquid chromatography with diode array detector (HPLC-DAD) and evaporative light scattering detectors (HPLC-ELSD) chromatograms, including 22 common peaks, and to conduct pharmacodynamic experiments on the anti-ulcer effects in animals. Gray Regression Degree Analysis (GRGS) was used to build the spectrum-effect relationship between fingerprint and AUA of Radix Astragali. The relationship between chemical constituents and pharmacological effect were revealed and tested by cell level. Then the pharmacokinetic and tissue distribution of seven AUA compounds were studied in rats. In this paper, the anti-gastric ulcer activity, quality control method, therapeutic basis, pharmacokintics and tissue distribution on the active constituents of Radix Astragali were studied. A reasonable evaluation system of Radix Astragali quality was discussed and a research thought route and method of quality evaluation system about TCM was provided.The first part of this paper was the literature review. The second part studied the spectrum-effect relationship between fingerprints and anti-gastric ulcer effects in Radix Astragali. The third part studied the pharmacokinetic and tissue distribution of seven anti-gastric ulcer activity compounds in rats. The major study methods and results were as follows:1. The spectrum-effect relationship between fingerprints and anti-gastric ulcer effects in Radix Astragali was studied. The best effective part was screened from five different polar parts by the anti-ulcer experiments in animals. Ten batches of ERA (95% ethanol extracts of RadixAstragali) samples from different geographic regions were used to conduct pharmacodynamic experiments on the anti-ulcer effects in animals, and to create the fingerprints, and to identify 16 common compositions, then to determine the contents of 16 compounds. The spectrum-effect relationship was built using gray relation statistics between the data of the pharmacodynamic and the contents of the compounds, and the active ingredients of anti-gastric ulcer activity in Radix Astragali were expounded and tested on cultured immortalized human gastric epithelial mucosa (GES-1) cells in vitro. The active anti-gastric ulcer substances identified using the spectrum-effect relationship with the gray relation statistics was verified at the molecular level. At the same time the paper revealed therapeutic basis for anti-gastric ulcer effects in Radix Astragali, and provided the reference about screening of active ingredients and spectrum efficiency relations research for other TCM.2. The pharmacokinetic and tissue distribution of seven anti-gastric ulcer activity compounds were studied in rats, and some valuable profiles were found. The paper was for the first time to study on the pharmacokinetics of astragaloside Ⅱ and astragaloside Ⅲ in rat plasma and tissues distribution of astragaloside Ⅱ, calycosin and formononetin. The disposition of calycosin-7-O-β-D-glucoside, calycosin, ononin, formononetin, astragaloside Ⅳ, astragaloside Ⅱ and astragaloside Ⅲ in the rat stomach suggested that the seven bio-active components are the main therapeutic substances for anti-gastric ulcer effects in Radix Astragali.The tissue distribution study showed the overall trend of disposition of these saponins compounds and isoflavone compounds were Cspleen> Cstomach>Cthymus> Clung> Cliver>Ckidney > Cheart> Ctesticle by the oral administration of Zhenqi Fuzheng capsules (ZFCs). The high levels of seven bio-active components observed in the spleen and thymus indicated that these components accumulated in organs involved in immune responses and showed that these organs were the major target sites in vivo.This paper explored a new method of screening active ingredient of anti-gastric ulcer activity in Radix Astragali, built the fingerprints of anti-gastric ulcer effect, made the spectral peak representing the chemical compositions to correspond with the anti-gastric ulcer effect, and illuminated the therapeutic basis for anti-gastric ulcer effects in Radix Astragali. The pharmacokinetics and tissue distribution of seven effective components in Radix Astragali and its preparation were studied. It provided a theoretical basis for studying the therapeutic basis of Radix Astragali and its preparation, mechanism, the rational use of drugs and the further development and utilization of Radix Astragali.