Effects of curcumin on JAK2-STAT3 signaling pathway in mice with immunological liver injury

Abstract

Objective To explore the protective effects and underlying mechanisms of curcumin in concanavalin A ( Con A) induced acute immu-nological liver injury in mice. Methods Sixty mice were randomly divided into control group, model group, bifendate group, curcumin 100, 200, 400 mg.kg-1group, each with 10.The drug was administered once a day for 7 days.One hour after the last administration, the mice in the blank control group were given the same dose of normal saline, and the other groups were injected with ConA15 mg.kg-1 in the tail vein.After 8 hours, serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels were measured in mice and liver index was calculated.Hepatic histopathological changes were observed by HE staining.Tumor necrosis factor-α(TNF-α), interleukin (IL) -6, IL-1β expression in liver tissue was detected by enzyme linked immunosorbent assay(ELISA). Phosphorylated Janus kinase 2(p-JAK2), phosphory-lated signal transducer and activator of transcription 3(p-STAT3)protein expression in liver tissue were detected by Western blot. Results Compared with the blank control group, the serum levels of ALT and AST in the model group were significantly increased (F values were 37.89 and 24.91 respectively, both P values<0.05). Severe pathological damage of liver tissue was found in mice with massive necrosis and apoptosis of hepatocytes.The contents of TNF-α, IL-6 and IL-1β were significantly increased (F values were 19.75, 18.93 and 22.90 respectively, all P values <0.05). The above results indicate that the model was successful.Compared with the model group, the serum levels of ALT and AST in the middle and high dose groups of curcumin were significantly lower (F values were 31.58 and 20.97 respectively, both P values <0.05). The levels of TNF-α, IL-6 and IL-1β in liver tissue decreased (F values were 17.78, 18.01 and 18.97 respectively, all P values <0.05), and the expression levels of p-JAK2 and p-STAT3 protein were down-regulated (F values were 34.27 and 36.78 respectively, both P values<0.05). Conclusion Curcumin has a preventive effect on ConA-induced immune liver injury in mice, and its mechanism may be related to its regulation of JAK2/STAT3 signaling pathway. Key words: Curcumin; Immune liver injury; Concanavalin A; JAK2/STAT3 signaling pathway