Study On The Absorption And Metabolism Of Madecassoside In Rat

Objective:Centella asiatica (L.) Urb. can promote wound healing, remove scar, inhibit the formation of hypertrophic scar partly, etc. Madecassoside is one of the main component in Centella asiatica (L.) Urb. A preliminary study showed that bioavailability of madecassoside is poor. The purpose of this study is to reveal the main active form based on studying the properties of absorption in the stomach and small intestine of rats, explore the major metabolic pathways of madecassoside based on analyzing its metabolites which were produced in liver microsomes and intestinal microflora. This study can be used to develop a basis for a specific medicine which are very effective to burn and scald.Method:1. A HPLC-ELSD method was developed to determine madecassoside in perfusate by the experimental models of stomach and small intestine of rats.2. A LC-MS method was developed to analyze the metabolites of madecassoside which were produced in liver microsomes and intestinal microflora, reveal its main active form and explore its major metabolic pathways in vivo.Results:1. The absorption percentage of madecassoside in the stomach of rats for 2 hours was 34.18%. The absorption rate constant of madecassoside in duodenum, jejunum, ileum, colon were 2.01×10-2,1.42×10-2,1.26×10-2,0.99×10-2min-1 respectively. The absorption rate constant of madecassoside of different concentrations at 25,50,100μg·mL-1 were 9.09×10-3,8.40×10-3,9.07×10-3 min-1 respectively. The absorption rate constant of madecassoside of different PH at 6.0, 6.8,7.4 were 9.17×10-3,7.70×10-3,8.40×10-3min-1 respectively. The absorption rate constant of madecassoside in small intestine of bile duct ligated rats was 8.77×10-3 min-1 while bile duct non-ligated rats was 8.40×10-3 min-1.2. Three metabolites can be find in intestinal microflora incubation system while none of the metabolites can be find in liver microsomal incubation system.Conclusions:1. It has no significant effect to the absorption of madecassoside in different concentrations and pH in rats'small intestine. The absorption process of madecassoside belongs to first order processes and the major mechanism of absorption is passive diffusion. The main absorption site is small intestine and the best absorption site was duodenum. Moreover, inhibit P-glycoprotein has no obvious improvement to the absorption of madecassoside.2. The metabolic processes of madecassoside in intestinal microflora present multistep model which means saccharide group of madecassoside are hydrolyzed one by one until glucoside is transformed into aglycon. The metabolic stability of madecassoside in liver microsomes is good. The result of this study has a great significance to further understanding of madecassoside in the metabolism and the structural modification of madecassoside.