Identification, Metabolism And Pharmacodynamics Of Hepatoprotective Effective Substances Of Swertia Mussotii Franch

Zangyinchen (Swertia mussotii Franch) is widely used in the clinical treatmentof acute jaundice hepatitis, viral hepatitis, cholecystitis and other diseases andcontains xanthone, iridoid and triterpene compounds in China. In order to find out theactive chemical components of Zangyinchen and their pharmacological mechanism,we have carried out the following experiments.First, through the acute jaundice hepatitis model induced by alpha-naphthylisothiocyanate (ANIT), we have detemined that the total iridoids and xanthone (hereafterreferred to TIXS) extracted from S. mussotii is its major active component. Thepreparation parameters of TIXS are optimized by orthogonal optimization method.Second, thirteen compounds have been purified from the TIXS through silicagel column chromatography, sephadex gel chromatography and reversed phase silicagel column chromatography, and their structures are identified by NMR, MS andother spectroscopy methods. Furthermore, a qualitative method for measuring theTIXS has been developed with the Q-TOF approaches.Third, based on the rat ANIT experimental model, we have shown that the TIXSand its two main components (swertiamarin and swertianolin) significantly promotebile secretion and decrease serum levels of ALT,AST, APT, TBILand DBIL. Histopathological observations show that the TIXSapplication significantly reduces the pathological injury induced byANIT in the liverand bile ducts.Fourth, through in vitro metabolic studies, we have shown that the TIXS can bepartly metabolized in intestinal bacteria to be swertimarin, gentianine,mangiferin, swertianolin and1,5,8-trihydroxy-3-methoxy xanthone (swertianolin aglycone). Swertianolin and1,5,8-trihydroxy-3-methoxy xanthone are absorbed by Caco-2cells more easily than swertimarin andgentianine. Furthermore, swertianolin can be partly metabolized to be1,5,8-trihydroxy-3-methoxy xanthone in the hepatomicrosome model.Fifth, in vivo metabolic studies indicate that24hours after administration of TIXSin rats, urine samples contain swertiamarin, mangiferin, swertianolin,1,5,8-trihydroxy-3-methoxy xanthone and other second-phase metabolites. This is consistent with our in vitro metabolic results of the TIXS.Sixth, both swertiamarin and gentianine manifest non-mutagenicity andanti-mutagenicity. Swertianolin and1,5,8-trihydroxy-3-methoxy xanthone alsoshow anti-hepatitis B virus activity.In summary, TIXS and its two main components (swertiamarin and swertianolin)both had remarkable promoting the secretion of bile, decreasing hematoidin andhepatoprotective effect. After oral administration of TIXS, it could metabolizepartly. Pharmacodynamic test showed both original components and their metaboliteshad good biological transitivity. Thus, TIXS can be primarily determined to theimportant effective material basis of Swertia mussotii Franch. The pharmacodynamicaction was achieved by the collaboration of both original components and theirmetabolites.