The Protective Effect And Mechanism Of Tibetan Medicine Zha Xun On Experimental Liver Injury In Mice

Objective:Tibetan medicine Zha Xun,is the commonly used drug in traditional Tibetan medicine for treatment of stomach heat,hepatic heat,nepropyrexia and other febrile illnesses.It was recorded by the Tibetan medicine book《Somaratsa》,which was written around the 8th century AD,that Zha Xun“can dry up bloody pus,indicate liver diseases,clear the heat,and induce cold syndrome”.It was also recorded in《Lun Shuo Xu》that Zha Xun had evident effect of clearing liver heat.In the clinical practices of Tibetan medicine,prescription preparations like“Jiuwei niuhuang pellet,Wuwei Zha Xun pellet（Tibetan name:Zha Xun abaribu）”which were used to treat hepatic fever containing Zha Xun,and the accurrence requency of Zha Xun in Tibetan medicine prescriptions for hepatic heat treatments ranked sixth.Thus it can be seen that Zha Xun has definite therapeutic effects on liver diseases.But currently we haven’t seen any related reports of the pharmacodynamics research of Zha Xun domesticly.So we use Concanavalin A（Con A）to induce acute immune liver injury model,use paracetamol（APAP）to make acute drug-induced liver injury model,use carbon tetrachloride（CCl₄）to make acute chemical-induced liver injury model for the investigation of the protective effect and mechanism of Zha Xun and its substitutes,n-butanol fraction from Zha Xun on liver injury in mice.Hence to provide a scientific basis for the radically reform,clinical application,preparation research,and resources development.Methods:（1）The experimental mice were injected with Con A of 20 mg·kg^-11 via the tail vein to establish the acute immune liver injury model,intraperitoneal injection with 250 mg·kg^-11 APAP to establish acute drug-induced liver injury model,intraperitoneal injection with 0.2%CCl₄ to establish acute chemical liver injury model,serum ALT and AST levels were detected to study the hepatoprotective effect of Tibetan medicine Zha Xun and its substitutes and to to provide pharmacological evidence for the identification and tracement of its origin by comparing the pharmacodynamic differences of Zha Xun and its substitutes.（2）The experimental mice were injected with Con A of 20 mg·kg^-11 via the tail vein to establish the acute immune liver injury model.N-butanol fraction from Tibetan medicine Zha Xun was given 7 days successively,to investigate its influences of the serum ALT,AST,TNF-αand IFN-γconcentrations,SOD,MDA contents,Caspase-3,Caspase-8 activities,and TNF-α,iNOS,NF-κB expressions.（3）Intraperitoneal injection with APAP 250mg·kg^-11 to establish the acute drug-induced liver injury model.N-butanol fraction from Tibetan medicine Zha Xun was given 7 days successively,to investigate its influences of the serum ALT,AST concentrations,liver SOD,MDA contents.（4）Intraperitoneal injection with 0.2%CCl₄-arachis oil to establish the acute chemical-induced liver injury model.N-butanol fraction from Tibetan medicine Zha Xun was given 7 days successively,to investigate its influences of the serum ALT,AST concentrations,the liver TNF-α,IL-1β,IL-6,SOD,MDA contents.Results:（1）The serum levels of ALT and AST were significantly decreased in mice with three kinds of liver injury models（p<0.05）,and its substitutes could significantly reduce the serum ALT and AST levels in the liver injury model induced by CCl₄（p<0.01）.（2）102.90、205.80 mg·kg^-11 of n-butanol fraction from Zha Xun can significantly reduce the liver index in ConA-induced acute immune liver injury mice.N-butanol fraction from Zha Xun could significantly reduce the activities of ALT,AST in serum（p<0.01）,decrease the serum content of TNF-αand IFN-γ（p<0.05）,reduce the levels of Caspase-3,Caspase-8 activities and hepatic MDA activities（p<0.05）of liver tissues,increase the hepatic SOD contents（p<0.05）,decrease TNF-α,iNOS,NF-κB expressions（p<0.05）.（3）N-butanol fraction from Zha Xun could decrease the liver index of the APAP-induced acute liver injury mice,but not significant（p>0.05）.102.90、205.80 mg·kg^-11 of n-butanol fraction from Zha Xun could significantly reduce the serum ALT,AST and liver MDA content in mice,increase SOD activities（p<0.05）.（4）102.90、205.80 mg·kg^-11 of n-butanol fraction from Zha Xun could significantly reduce the liver index of CCl₄-induced acute liver injury mice（p<0.05）,reduce the serum ALT,AST and increase SOD activities,and205.80 mg·kg^-11 could aslo reduce MDA content in liver tissue.All dose groups could significantly reduce the contents of TNF-α,IL-1β,IL-6 in serum（p<0.01）.Conclusion:Zha Xun and its substitutes are not equal in clinical use.The n-butanol fraction of Tibetan medicine Zha Xun,as the pharmacodynamic material basis,plays a hepatoprotective effect.The mechanism may be is its inhibition effects to the inflammatory factors release,the oxidative stress,and the apoptosis.