Study On Protective Effects And Mechanisms Of Tarazasterol On Liver Injury Induced By APAP In Mice

Taraxasterol is a pentacyclic triterpenoid compound isolated from Taraxacum officinale.Its anti-inflammatory,anti-oxidation,anti-tumor and other biological functions have been widely concerned in recent years.In this study,acetaminophen(APAP)-induced mouse liver injury model was established to explore the protective effects and mechanism of taraxasterol on liver injury in mice,so as to provide a new theoretical basis for the clinical use of taraxasterol and a new idea for the treatment of drug-induced liver injury in miceThe 8-week-old mice were randomly divided into 6 groups:NT group,model group(APAP-induced group),positive group(Bifondate Pills,Bif)and taraxasterol groups(10,5,2.5 mg/kg).Mice were given daily doses of taraxasterol,the positive group was given 200 mg/kg of Bif suspension,and NT group and model group were given 0.5%sodium carboxymethylcellulose solution by gavage.After 7 d of continuous administration,the mice were fasted for the last time.Followed by intraperitoneal injection of 300 mg/kg APAP solution 1 h later,the mice were killed after eyeball blood collection,and the liver tissues were collected for subsequent experiments.Weight changes of mice were calculated,the contents of ALT and AST in sera and the contents of GSH,SOD,MDA and ROS in liver were determined.The inflammatory infiltration and necrosis in liver were observed by H&E staining and the apoptosis of hepatocytes in liver tissue was observed by TUNEL staining.The contents of IL-1 β,TNF-α and IL-6 in liver were determined by ELISA and the expression of IL-1β,IFN-γ,TNF-α,IL-6 and IL-4 mRNA were determined by qRT-PCR.The proteins expression of JNK,Nrf-2/HO-1,Bax/Bcl2/caspase3,PI3K/AKT/mTOR in liver was detected by Western blot.The results showed that taraxasterol could significantly or extremely significantly reduce the liver index,the contents of ALT and AST in sera and the contents of MDA and ROS in liver tissues compared with APAP group.At the same time,the contents of GSH and SOD were significantly or extremely significantly up-regulated in liver tissues of the mice with APAP-induced liver injury.Taraxasterol could also significantly or extremely significantly inhibit the secretion of TNF-α,IL-6,IL-1β and IFN-γ,and increase the expression of anti-inflammatory factor IL-4 in the liver.It could significantly down-regulated the expression of Nrf2/HO-1 protein,the ratio of Bax/Bcl-2 and caspase3,P13K/AKT/mTOR protein in liver tissues.Conclusions:the above results show that taraxasterol can inhibit the expression of inflammatory factors,oxidative stress and apoptosis by reducing the activity of ALT,AST and other enzymes,increasing the activity of antioxidant enzymes,reducing the occurrence of lipid peroxidation and regulating the expression of JNK,Nrf-2/HO-1,Bax/Bcl2/caspase 3,PI3K/AKT/mTOR signal pathway proteins,so as to protect the liver injury in mice induced by APAP.This experiment will provide a new idea for the treatment of APAP-induced liver injury and a theoretical basis for the application of taraxasterol in the treatment of liver injury.