Basic Study On Over-dose Used Reason Of Radix Paeoniae Rubra Curing Acute Cholestasis Hepatitis Based On The Pharmacokinetics

Cholestatic hepatitis is a common and frequently encountered disease. It is likely to induce liver cirrhosis or liver cancer and will lead to serious consequences If not effectively treated. Wang et. Has innovatively used cute method of cooling and activating blood with using the high-dose of Radix Paeoniae Rubra(150g) in Integrative Medicine Center of302Military, which has been gained considerable attention due to its significant hepatoprotective effect. However, Radix Paeoniae Rubra over-dose used of reason is still unclear. We are being to explore the possible therapeutic basis and the reason of heavy dosage by applying the method of the serum pharmacochemistry of Chinese medicineand, pharmacodynamics and pharmacokinetics. The main results are summarized below:1. Analysis of the constituents in vitroThe composition of the extract of Radix Paeoniae Rubra was analysised,15chemical composition were revealed in PRP objectively, Which had layed the foundation for serum pharmacochemistry of RPR.2. Analysis of the constituents in vivoBased on Serum Pharmacochemistry of TCM,4constituents absorbed into blood,5constituents absorbed into bile,10constituents absorbed into urine after administration of RPR respectively, and paeoniflorin and albiflorin were isolated and identified in the serum, bile and urine respectively. It helped to clarify the efficacy of the material basis of RPR and pharmacodynamic mechanisms.3. Pharmacological studyThe protective effect of paeoniflorin and albiflorin against a-naphthylisothiocya-nate-induced liver injury in rats was studied. We verified that paeoniflorin and albiflorin had remarkable effect on liver protection and enzyme descending based on the biochemical detection and organizations.4. Pharmacokinetic studyWe comparatively studied the pharmacokinetic of paeoniflorin and albiflorin after oral administration of RPR in normal rats and the acute cholestasis hepatitis rats. The results showed that among most calculated parameters including AUC0-t, AUC0-8, tmax and CLz/F, which were significant differences between the normal rats and the acute cholestasis hepatitis rat groups. And blood concentration in model rats was higher than in normal rats. 5. Bioavailability studyBioavailability of paeoniflorin and albiflorin in the normal rats was2.528%and1.785%, However7.111%and6.382%in model rats respectively. Which had explained the scientific basis of RPR with over-dose used.According to above results, it can be concluded that paeoniflorin and albiflorin were the herapeutic basis against a-naphthylisothiocyanate-induced liver injury in rats. The reasons of heavy dosage were low bioavailability and disease factors. The results of investgations above supported experimental data for heavy dosage of PRP and had layed foundation for research and development of TCM components.