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Studies On Pharmacokinetics And The Relation To Intestinal Bacteria Of Huangqin-Tang Decoction

Posted on:2003-12-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:F ZuoFull Text:PDF
GTID:1104360062991001Subject:Integrative basis
Abstract/Summary:PDF Full Text Request
In our previous studies, by using a high-performance liquid chromatographic (HPLC) method which was established in our laboratory, the metabolites in both the compound prescription and all the single herb decoctions were identified and determined both qualitatively and quantitatively. It could be found that the constituents of Huangqin-Tang, induing baicalin (baicalein 7-glucuronide; BG), wogonoside (wogoninoglucuronide; WG), oroxylin-A-glucuronide (OG) from Scutellariae Radix, paeoniflorin (PF) from Paeoniae Radix, liquiritin (liquiritigenin 4'-O-glucoside; LG), isoliquirtin (isoliquiritigenin 4-glucoside; ILG) and glycyrrhizic acid (GL) from Glycyhhizea Radix, were converted to their metabolites baicalein (B), wogonin (W), oroxylin-A (0), paeonimetabolin-I (PM-I), liquiritigenin (L), isoliquiritigenin (IL) and glycyrrhetinic acid (GA) by intestinal bacteria in vitro. And the results suggested that the metabolism of most glycosides was improved in the compound prescription. In the present paper, the pharmacokinetic study of Huangqin-Tang in rats, and the relation between intestinal bacteria and metabolism in vivo of Huangqin-Tang decoction were performanced. The experiments were carried out in the fields as follows:1. The metabolism of constituents of Huangqin-Tang decoction in conventional, germ-free and gnotobiote miceGerm-free animals infected certain bacteria to establish the gnotobiote mice, which be used in the study of the metabolism effects of intestinal flora in vivo. In this test, the metabolic fate of the constituents of Huangqin-Tang decoction by intestinal bacteria was investigated using conventional, germ-free and gnotobiote mice (E. aerofaciens-infected and L. fermentum-infected). After oral administration of Huangqin-Tang, the cecal contents and cumulative feces were analyzed by HPLC method.The constituents of Huangqin-Tang decoction in the cecal contents or feces were not metabolized in germ-free mice through out the experiment. However, the metabolites of the constituents of Huangqin-Tang decoction were detected both in conventional and two kinds of gnotobiote mice, which were similar to those metabolized by human intestinal bacteria in vitro.2. The comparison of pharmacological effects between Huangqin-Tang decoction and their metabolites by human intestinal bacteria2.1 The protective activity of liver injury induced by D-galactosamine(GalN)Using the pseudogerm-free (conventional animals treated with various antibiotics) and conventional animals, the hepatoprotection effects in vivo between Huangqin-Tang decoction and metabolites were compared. The liver injuries in conventional and pseudo-germfree mice were induced by GalN. After oral administration of Huangqin-Tang or their metabolites, the serum transaminase (ALT and AST) activities were detected.In pseudo-germfree mice, the metabolites significantly reduced ALT levels. However, Huangqing-Tang didn't affect the ALT levels in this kind of mice. It indicated that the metabolites had a more potential hepatoprotection effect than Huangqin-Tang decoction in pseudo-germfree mice.2.2 The antibacterial activity in vitro and in vivo.The antibacterial tests in vitro and in vivo were performed by agar dilution method and lethal protection of animal respectively.The antibacterial activity of metabolites of Huangqin-Tang to Salmomella, Dysentery bacillus and Proteus in vitro was stronger than Huangqin-Tang decoction. The metabolites of Huangqin-Tang had lethal protection to the animals, which were infected by Staphylococcus aureus and Escherichia coll respectively, whereas Huangqin-Tang had no lethal protection effect.All the results from the pharmacological effect tests suggested that intestinal bacteria played an important role in the metabolism of Huangqin-Tang decoction in vivo, and the metabolites of the constituents in Huangqin-Tang decoction by intestinal bacteria were the real active components in vivo. 3. Pharmacokinetics study of Huangqin-Tang decoction in rats3.1 The gastrointestinal absorption and tran...
Keywords/Search Tags:Huangqin-Tang decoction, pharmacokinetics, intestinal bacteria
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