OBJECTIVE To explore the potential mechanism of Cigu Xiaozhi Prescription (CGXP) in the treatment of non-alcoholic steatohepatitis (NASH) liver fibrosis.

METHODS A NASH mouse model was established. The degree of liver enlargement was evaluated by calculating the liver index. Hematoxylin - eosin (HE) and Masson staining were used to observe the degree of liver fibrosis. In addition, immunohistochemistry was employed to detect the expression of liver fibrosis - related proteins, including α - SMA, Collagen 1, MMP2, and MMP9. Western blot and qPCR techniques were used to detect the expression levels of HIF - 1α, E-cadherin, N-cadherin, Shh, Smo, Gli1, and Gli2 in the mouse liver. The alkaline hydrolysis method was used to measure the content of liver hydroxyproline.

RESULTS CGXP could effectively reduce the liver index (P < 0.001), alleviate liver enlargement and inflammation, and significantly improve the pathological damage of liver tissue in mice with liver fibrosis. CGXP significantly decreased the expression levels of liver fibrosis-related proteins α-SMA, Collagen 1, MMP2 and MMP9 (P < 0.01, P < 0.000 1); reduced the levels of HIF - 1α, E - cadherin, N - cadherin, Shh, Smo, Gli1, and Gli2, and the therapeutic effect of high - dose CGXP was particularly significant (P < 0.05, P < 0.01, P < 0.001, P < 0.000 1).

CONCLUSION CGXP can relieve NASH liver fibrosis in mice by reducing the liver index, alleviating inflammation, and improving tissue pathological damage. The mechanism may be related to the inhibition of the Hedgehog signaling pathway, which alters the activation and proliferation of hepatic stellate cells and reduces the synthesis and deposition of extracellular matrix.