Abstract:Objective To investigate the mechanism of action of Gandouling in the intervention of liver epithelial-mesenchymal transition (EMT) in rats with copper overload-induced liver fibrosis by inhibiting the Notch signaling pathway. Methods A total of 40 male Sprague-Dawley rats were randomly divided into normal group, model group, and low-, middle-, and high-dose Gandouling groups. The rats in the normal group were given normal diet, and those in the other groups were given copper sulfate diet to establish a rat model of copper overload-induced liver fibrosis. Serum levels of alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), alkaline phosphatase (ALP), and hyaluronic acid (HA) and the content of hydroxyproline (Hyp) in liver tissue were measured. Hematoxylin and eosin staining and Masson staining were used to observe liver pathological injury and collagen deposition. RT-PCR was used to measure the mRNA expression of transforming growth factor-β1 (TGF-β1), Jagged1, Notch1, Notch3, and Snail in liver tissue, Western blot was used to measure the protein expression of Hes1 and E-cadherin, and immunohistochemistry was used to measure the expression of alpha-smooth muscle actin (ɑ-SMA). Results Compared with the normal group, the model group had significant increases in serum levels of ALT, AST, ALP, and HA, the content of Hyp and collagen fibers in liver tissue, the mRNA expression of TGF-β1, Jagged1, Notch1, Notch3, and Snail in liver tissue, and the protein expression of Hes1 and ɑ-SMA in liver tissue (P<0.05) and a significant reduction in the protein expression of E-cadherin (P<0.05). Compared with the model group, the middle- and high-dose Gandouling groups had a significant increase in the protein expression of E-cadherin (P<0.05) and significant reductions in all the other indices (P<0.05). Conclusion Gandouling exerts an interventional effect on EMT by inhibiting the Notch signaling pathway and can alleviate liver fibrosis by reducing the transformation, activation, and proliferation of myofibroblasts and the accumulation of collagen fibers.