The Study Of Protection Effect On Acute Liver Injury Of Rabdosia Serra (Maxim.) Hara And Itspharmacodynamic And Pharmacokinetic Behaviour

ObjectiveThe purpose of study was to explore Rabdosia serra (Maxim.) Hara induced Protective effect and mechanism of liver and the expression of FXR、MRP2 and BSEP on experimental model of Intrahepatic Cholestasis rats induced by ANIT.Methods1. To observe acute toxicity of Xihuangcao and Rosmarinic acid.Mice were given the maximum concentration of Rabdosia serra (Maxim.) Hara or rosmarinic acid. After that, they were feeded and observed for 14d. All mice were dissected for histopathological examination.2. By Applicatting HPLC to detect main chemical components and its extraction technology of Rabdosia serra (Maxim.)To establish a simple, rapid and sensitive HPLC method for five major water-soluble components of Rabdosia serra (Maxim.) in biological samples,and the effect and stability of the method are confirmed. Comparison of distilled water reflux extraction, extracted with methanol 50% ethanol extract,70% ethanol extract and 95% ethanol extrac. From the 5 extraction process, we initially identified the optimal extraction method to extract Rabdosia serra (Maxim.) main active ingredient.3. To observe interventive effect of Rabdosia serra (Maxim.) and Rosmarinic acid. on experiental rat model of cholestasis induced by ANIT. Animal models of intrahepatic cholestasis was established with ANIT at 80mg·kg-1. Sprague Dawley rats were randomly divided into 9 experimental groups, namely normal control group, modle group, low-, middle- and high-dosage Rabdosia serra (Maxim.) groups (25g, 40g,80g·kg-1 respectively), low-, middle- and high-dosage rosemary acid groups (25m g,50mg, 100mg·kg-1 respectively), and ursodeoxycholic acid(UDCA) group (100mg·kg-1), After intra-gavage administration for 7 day, the rats were suffered bile duct surgery and the bile composition, the bile rate, serum enzyme indicators of liver function and antioxidant enzymes in the serums and the livers were tested. Meanwhile the pathological examination of liver and the genes or protein expression of FXR, MRP2 and Bsep were also observed.4. The study on the pharmacokinetics of Rosmarinic acid and Pharmacokinetic-pharmacodynamic model in ratsEstablish a rational, simple and sensitive method for detecting a biological sample rosemary acid content determined by HPLC, and Oral and intravenous plasma concentration was measured at various time points, Pharmacokinetic param-eters were calculated and established PK-PD-pharmacokinetic-pharmacodynamic model for further study of the impact of drug plasma concentration on the efficacy mechanism.ConclusionIn the ANIT-induced cholestasis liver injury model, Xihuangcao can improve liver function, increase antioxidant enzyme levels, recover ingredients bile, promote bile secretion, and restrain inflammation of liver cells (such as mitochondria and other organelles important) Molecular mechanisms by which upregulate the expression of FXR gene protein, and further regulation BSEP and MRP2 protein expression in the liver and gallbladder.The performance above proved that Xihuangcao has good effect on protection ofanti-cholestasis role.