Studies Of Salvianolica Acid Metabolish And Penetrate The Blood-brain Barrier

Salvia is dried roots and rhizomes of Salvia.There are two main kind of chemical components in Salvia:fat-soluble tanshinone compounds and water-soluble phenolic compounds.Sal B is isolated from Salvia,which has very good protection on cerebral ischemia caused by cerebro vascular diseases. Sal B is also an important component of many indicators of salvia preparations.Sal B through the blood-brain barrier uneasily, while Danshensu distribute quickly in the organization, and can through the blood-brain barrier easily.In this paper,we study the metabolism of Sal B and compare the difference of vivo behavior of prime between Sal B and Danshensu.At the same time,we establish the vitro blood brain barrier to investigate the characteristics of Sal B and Danshensu penetrate the blood brain barrier. We also study the protective effect of both on PC12cells,which can provide the basis for the preparation of Salvia quality standards.Chapter1summary and analysis the chemical composition,ADME and drugs penetrate the blood-brain barrier.Chapter2study the metabolism of Sal B in vivo, using UPLC/Q-TOF technical analysis to identify the structural of metabolites.In plasma,there are two metabolites were identified,and ester bond cleavage is the major metabolites way; in bile there are five metabolites were identified,and ester bond cleavage and methylation are the major metabolites way;in urine,there are four metabolites were identified,methylation and sulfation are the major metabolites way. At the same time,we clarifies the metabolic pathway of the main metabolite in rats after intravenous injection of Sal B in the plasma,bile, urine,which reveals the variation of Sal B in rats.Chapter3study the difference of pharmacokinetics and plasma protein binding rate between Sal B and Danshensu.The results show that the maximum plasma concentration of Danshensu is significantly higher than that Sal B,and the average well time,half-life is significantly longer than that Sal B after inject same amount of acid B and Danshensu. We study the plasma protein binding rate of Sal B and Danshensu,to compare the difference between in vivo distribution behavior.Results show that Sal B and danshensu in three kinds of protein binding in plasma is different, and does not have concentration-dependent manner.The protein binding rate of Sal B significantly higher than Danshensu,which can reaction that Sal B is combined majority in the plasma state and has low free drug concentration,while Danshensu is counter.Chapter4establish the blood brain barrier in vitro to study acid Band Danshensu penetrate the blood brain barrier properties.The results show that, danshensu can through the blood-brain barrier,but Sal B fail to.The results suggest that Danshensu can penetrate the blood brain barrier,but Sal B can not.Chapter5study the protective effect on PC12of Sal Band Danshensu,to explore its possible mechanism.We study the LDH leakage rate and intracellular ROS levels to clarify mechanism.Preliminary studies indicate that Danshensu can significantly reduce the accumulation of glutamate-induced PC12cell injury LDH leakage rate and intracellular ROS.Chapter6summary all the work and look forward to the future.