E Se tea extract ameliorates CCl4 induced liver fibrosis via regulating Nrf2/NF-κB/TGF-β1/Smad pathway

Background: Liver fibrosis is a crucial progress to deteriorate liver disease. E Se tea (ES) is an ethnic herbal tea in China that has various biological activities for human beings. However, the traditional application on the treatment of liver disease is not studied. Purpose: This study is firstly performed to explore the chemical constituents of ES extract together with its antihepatic fibrosis effect and potential mechanism on CCl4 treated mice. Study design and methods: The chemical constituents of ethanol-aqueous extract from ES (ESE) were analyzed by UPLC-ESI-MS/MS. The anti-hepatic fibrosis effect of ESE was determined by measuring ALT and AST activities, antioxidative indexes, inflammatory cytokines and collagen protein levels on CCl4 treated mice. Moreover, H&E, Masson staining and immunohistochemical analysis were performed for evaluating the protective effect of ESE on histopathological changes of liver tissues. Results: UHPLC-HRESI-MS/MS analysis showed that the ESE was rich in flavonoids such as phlorizin, phloretin, quercetin and hyperoside. ESE could significantly reduce the plasma AST and ALT activities. The cytokines (IL-6, TNF-alpha, IL-1 beta) expressions were inhibited after ESE administration via suppressing NF-kappa B pathway. In addition, ESE could decrease MDA accumulation for alleviating CCl4 induced liver oxidative stress via regulating Nrf2 pathway to promote the expressions of antioxidant enzymes (SOD, HO-1, CAT and NQO1). Moreover, ESE could inhibit the expressions of TGF-beta 1, Smad2, alpha-SMA, and collagens I and III proteins, thereby effectively alleviate the liver fibrosis. Conclusion: This study demonstrated that ESE could alleviate liver fibrosis through enhancing antioxidant and anti-inflammatory abilities by Nrf2/NF-kappa B pathway and reducing deposition of liver fibrosis via suppressing TGF beta/Smad pathway.