β-sitosterol relieving realgar-induced liver injury in mice through PI3K/Akt signaling pathways
Objective:To explore the effect and mechanism of β-sitosterol on realgar-induced liver injury in mice.Methods:The mice were divided into control group,model group,positive control group (bifendate),low-doseβ-sitosterol group,middle-doseβ-sitosterol group and high-doseβ-sitosterol group.Except for the control group,the other groups of mice established realgar-induced liver injury models.After 14 days of drug intervention,HE staining was used to detect the liver injury,and the liver function indicators Alanine aminotransferase (ALT)and Aspartate aminotransferase (AST)were detected.ELISA was applied to detect the levels of inflammatory factors[Tumor necrosis factor (TNF-α),Interleukin1β(IL1-β),IL-6],and kit was adopted to detect the liver tissue oxidative stress indicators[Malondialdehyde (MDA),Superoxide dismutase (SOD),Glutathione peroxidase (GSH-Px)].Western blot was used to detect the related protein expressions of PI3K/AKT signaling pathways.The above same indicators were detected after intervention with Phosphatidylinositol kinase 3 (PI3K)/protein kinase B (Akt)pathways activator SC79.Results:Compared with the model group,the positive control group,the middle-dose β-sitosterol group,and the high-dose β-sitosterol group showed varying degrees of improvement in liver tissue damage in mice.Levels of serum ALT,AST,TNF-α,IL-1β,IL-6,and hepatic MDA were significantly reduced(P<0.05),while hepatic SOD and GSH-Px levels were significantly increased (P<0.05 ).Additionally,the ratios of p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR were significantly decreased(P<0.05).Furthermore,β-sitosterol was able to reverse the exacerbation of these indicators caused by intervention with the AKT agonist SC79 (P<0.05 ).Conclusion:β-sitosterol inhibits the activation of PI3K/Akt signaling pathways to reduce serum inflammatory response and relieve oxidative stress in mice with realgar-induced liver injury,and it has a protective effect on liver tissue.