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 a variety of biological activities. However, it remains unknown whether SP has an effect on ameliorative nonalcoholic fatty liver disease (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 an 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 inhibited the hepatic injury and lipid steatosis by decreasing the levels of ALT, AST, TG and TC in vitro and vivo. The SPE suppressed the oxidative stress and inflammation by restraining the generation of ROS, MDA, IL-1β, IL-6 and TNF-α and enhancing the activity of antioxidant enzymes including SOD, CAT and GSH-Px in NASH model. Moreover, SPE declined the level of fibrosis markers including HYP, Col Ⅰ and α-SMA in HFD combined CCl₄ (HC)-induced mice. Mechanically, SPE inhibited hepatocellular Keap1 expression and promoted Nrf2 nuclear translocation, which suppressing the phosphorylation of IκBα/NF-κB. In addition, SPE down-regulated the level of 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/NFκB 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.