N-Acetyl-l-tryptophan inhibits CCl4-induced hepatic fibrogenesis via regulating TGF-β1/SMAD and Hippo/YAP1 signal

Background Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl- l -tryptophan ( l -NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l -NAT on liver fibrosis is not determined. Purpose The present study investigated the effect of l -NAT on liver fibrosis and explored it potential molecular mechanism. Methods To address this concern, this study was carried out via fibrotic mice model induced by CCl 4 and many approaches such as various histological staining methods, western blot assay, etc. Result l -NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl 4 ). Histological staining showed that l -NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l -NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l -NAT inhibited the expressions of TGF-β1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl 4 -induced liver fibrosis. Conclusion These results clearly demonstrated that l -NAT attenuated CCl 4 -induced liver fibrosis in mice, and this protective mechanism might relate to TGF-β1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.