PHARMACOKINETIC STUDY OF STANDARDIZED EXTRACT OF CENTELLA ASIATICA ECa 233 IN RATS

Abstract

The standardized extract of Centella asiatica ECa 233 is consist of triterpenoid glycosides, which are madecassoside (53.1%) and asiaticoside (32.3%). This extract has been found to exhibit various positive pharmacological effects on the central nervous system, and have a good safety profile in both acute and sub-chronic toxicity studies. The present study aimed to explore the disposition kinetics of ECa 233 in rats. The extract was intravenously or orally administered at doses from 50 to 200 mg/kg. Plasma, tissues, urine, and feces were collected at time points from zero to 48 h after dosing. The levels of madecassoside and asiaticoside, as well as their postulated triterpenic metabolites – madecassic acid and asiatic acid – in biological samples, were simultaneously measured by liquid chromatography-tandem mass spectrometry. The results showed that all animals had good tolerability for ECa 233. Whereas madecassic and asiatic acids were found in negligible amounts after pharmacokinetic assessment, madecassoside and asiaticoside demonstrated rather similar absorption and tissue distribution profiles. They were rapidly absorbed, reaching maximum levels within 5-15 minutes after oral administration, but they had poor oral bioavailability, less than 1%. Both triterpenoids were extensively distributed in the brain, stomach, and skin within 1 h and remained there for at least 4 h after dosing. A negligible amount of madecassic acid and asiatic acid were found in plasma and tissues, despite these two metabolites were extensively detected in feces after dosing. The pharmacokinetic results obtained could provide some guidance for appropriate dosing regimen of ECa 233 in future studies. This study also provided the first evidence demonstrating the distribution of madecassoside and asiaticoside to their target tissues from oral administration.