Protective effect of luteolin on liver function in rats with autoimmune hepatitis and its mechanism

LAI Xijie; LIN Liwei; LIU Hongliang; LI Hongshan

doi:10.13431/j.cnki.immunol.j.20240059

Abstract：To assess the protective effects of luteolin(LT)on liver fibrosis in rats with autoimmune hepatitis(AIH)and to explore the underlying mechanisms,total of 62 rats were recruited and randomly divided into normal control group(CT),AIH model group(AIH),LT low-dose group(LT L),LT medium-dose group(LT M),LT high-dose group(LT H)and prednisolone group(PSL),with 10 rats in each group.The rat in CT group were injected with an equivalent volume of physiological saline via the tail vein,when the rat in the other groups were received tail vein injection of concanavalin A(Con A)dissolved in physiological saline to induce the AIH model.Then,the rat in LT L,M,and H groups were administered intraperitoneal injections of LT dissolved in physiological saline(at doses of 5,25,and 50 mg/kg,respectively),and the rat in the PSL group received intraperitoneal injections of PSL dissolved in physiological saline(at a dose of 10.0 mg/kg),while the rat in the CT and AIH groups received equivalent volumes of physiological saline intraperitoneally.All treatments were administered twice daily for 7 consecutive days.The day after the last treatment,liver function indices,peripheral blood lymphocyte subsets,and hepatic hydroxyproline content were measured.Furthermore,Masson staining was used to assess the liver fibrosis was assessed using,and Western blot analysis was performed to detect the expression levels of activated nuclear factor κB(NF-κB),phosphorylated NF-κB(p-NF-κB),inhibitor of nuclear factor κBα(IκBα),and phosphorylated IκBα(p-IκBα)proteins in liver tissue.Compared to the CT group,the AIH group exhibited significantly higher serum levels of alanine aminotransferase(ALT),total bilirubin(TBIL),CD4+T lymphocyte ratio,CD4+/CD8+ratio,and hepatic hydroxyproline content(P<0.05),while albumin(ALB)levels and the CD8+T lymphocyte ratio were significantly lower(P<0.05).LT in all doses could reverse these changes mentioned above in AIH rats in a dose-dependent manner(P<0.05),and no significant differences were observed between the LT H group and the PSL group in these parameters(P>0.05).Masson staining results revealed that liver fibrosis in the LT groups was less severe than that in the AIH group,with a clear dose-dependent effect.The PSL group exhibited similar antifibrotic effects to the LT H group.Furthermore,the AIH group showed significantly higher levels of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios in liver tissue,as compared to the CT group(P<0.05),while LT could suppress the increase of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios(P<0.05)in a dose-dependent manner(P<0.05),and no significant differences in these ratios were observed between the LT H group and the PSL group(P>0.05).Taken together,Luteolin can improve liver function and immune function,and alleviate liver fibrosis by inhibiting the NF-κB pathway in AIH rats.