Syringa pubescens Turcz. ethyl acetate extract improves non-alcoholic steatohepatitis by regulating the Nrf2, IκBα and TGF-β1 signaling pathways

The flower of Syringa pubescens Turcz. (SP), was used as both medicine and food in China, exhibited various biological activities. However, it remains unknown whether SP affects ameliorative nonalcoholic steatohepatitis (NASH). In this study, the improvement of SP ethyl acetate extract (SPE) on NASH was evaluated and the potential mechanisms were explored. The glycosides of SPE were determined by HPLC method. HepG2 cell lines were treated with free fatty acid to clarify the improvement effect and mechanisms of SPE on NASH in vitro. C57BL/6J mice were treated by 60% kcal high-fat diet (HFD) combined with carbon tetrachloride (CCl₄) to establish the NASH model in vivo. The results showed SPE could inhibit the hepatic injury and lipid steatosis by decreasing the levels of alanine aminotransferase, aspartate aminotransferase, triglyceride and total cholesterol in vitro and in vivo. The SPE suppressed the oxidative stress and inflammation by restraining the generation of reactive oxygen species, malondialdehyde, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) and enhancing the activity of antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase in NASH model. Moreover, SPE declined the level of fibrosis markers including hydroxyproline, type I collagen and α-smooth muscle actin (α-SMA) in HFD combined CCl₄-induced mice. Mechanically, SPE inhibited hepatocellular Kelch like ECH associated protein 1 expression and promoted nuclear erythroid 2-related factor 2 (Nrf2) nuclear translocation, which suppressed the phosphorylation of IκBα/NF-κB. In addition, SPE down-regulated the level of transforming growth factor β1 (TGF-β1) and phosphorylation of Smad2 to mitigate fibrosis. In brief, SPE could significantly alleviate lipid accumulation, oxidative stress, inflammation and fibrosis via regulating Nrf2/HO-1, IκBα/NF-κB and TGF-β1/Smad2 pathways in the progression of NASH, which indicated that SPE had the potential to be a novel and effective drug or food supplements for the improvement of NASH.