Study on the effect Mongolian Medicine Qiwei Qinggan Powder on Hepatic Fibrosis through JAK2/STAT3 Pathway

Abstract Background: To study the anti-hepatic fibrosis effect and explore the mechanism of Qiwei Qinggan Powder (QGS-7) in vivo and in vitro. Methods: Carbon tetrachloride (CCl 4 )-treated rats and hepatic stellate cells (HSCs) were used. Alanine Aminotransferase (ALT), Aspartate transaminase (AST) and Alkaline Phosphatase (ALP) were detected in serum of rats in each group, hydroxyproline (HYP) was detected in liver tissue. Formalin-fixed liver specimens were stained with hematoxylin and eosin (H&E) reagent, Masson trichrome, and then analyzed. The expression of Alpha smooth muscle actin (α-SMA) in liver was detected by immunohistochemistry. The expression level of Collagen I, α-SMA, Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3(STAT3) mRNA were determined by real Time polymerase chain reaction (RT-qPCR). Meanwhile, the protein expression levels of α-SMA, Collagen I, JAK2, phosphorylation-JAK2 (p-JAK2), STAT3 and phosphorylation-STAT3 (p-STAT3) were determined by Western Blot. The proliferation of HSC was detected by MTT and the apoptosis was detected by flow cytometry. Results: QGS-7 treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of ALT, AST and ALP. Meanwhile, the HYP of liver was significantly decreased. Histopathological results indicated that QGS-7 alleviated liver damage and reduced the formation of fibrosis septa. Moreover, QGS-7 significantly attenuated expressions of α-SMA, Collagen I, JAK2, p-JAK2, STAT3, p-STAT3 relative mRNA and protein level in the rat hepatic fibrosis model and HSCs. And QGS-7 can inhibit HSCs proliferation and promote it apoptosis. Conclusion: Mongolian medicine QGS-7 has the effect of treating hepatic fibrosis and can inhibit the activation, proliferation and promote apoptosis of HSCs. Meanwhile, in the process of anti-hepatic fibrosis, QGS-7 can reduce the expression of JAK2, p-JAK2, STAT3 and p-STAT3 in JAK2/STAT3 signaling pathway. Therefore, we speculate that QGS-7 may affect HSCs through JAK2/STAT3 signaling pathway, so as to play an anti-hepatic fibrosis role.