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NOX4 and reactive oxygen species expressed in HSCs play an important role in liver fibrosis. Forsythiaside A (FA), a phenylethanoid glycoside extracted and isolated from Forsythiae Fructus, has significant antioxidant activities. However, it is not clear whether FA can play a role in inhibiting the HSCs activation through regulating NOX4\/ROS pathway. Therefore, our purpose is to explore the effect and mechanism of FA on HSCs activation to alleviate liver fibrosis. LX2 cells were activated by TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 <jats:italic>in vitro<\/jats:italic>. MTT assay and Wound Healing assay were used to investigate the effect of FA on TGF\u2010<jats:italic>\u03b2<\/jats:italic>1\u2010induced LX2 cell proliferation and migration. Elisa kit was used to measure the expression of MMP\u20101 and TIMP\u20101. Western blot and RT\u2010qPCR were used to investigate the expression of fibrosis\u2010related COLI, <jats:italic>\u03b1<\/jats:italic>\u2010SMA, MMP\u20101 and TIMP\u20101, and inflammation\u2010related TNF\u2010<jats:italic>\u03b1<\/jats:italic>, IL\u20106 and IL\u20101<jats:italic>\u03b2<\/jats:italic>. The hydroxyproline content was characterized using a biochemical kit. The mechanism of FA to inhibit HSCs activation and apoptosis was detected by DCF\u2010DA probe, RT\u2010qPCR, western blot and flow cytometry. NOX4 siRNA was used to futher verify the effect of FA on NOX4\/ROS pathway. The results showed that FA inhibited the proliferation and migration of LX2 cells and adjusted the expression of MMP\u20101, TIMP\u20101, COLI, <jats:italic>\u03b1<\/jats:italic>\u2010SMA, TNF\u2010<jats:italic>\u03b1<\/jats:italic>, IL\u20106 and IL\u20101<jats:italic>\u03b2<\/jats:italic> as well as promoted collagen metabolism to show potential in anti\u2010hepatic fibrosis. Mechanically, FA down\u2010regulated NOX4\/ROS signaling pathway to improve oxidation imbalances, and subsequently inhibited PI3K\/Akt pathway to suppress proliferation. FA also promoted the apoptosis of LX2 cells by Bax\/Bcl2 pathway. Furthermore, the effects of FA on TGF\u2010<jats:italic>\u03b2<\/jats:italic>1\u2010induced increased ROS levels and <jats:italic>\u03b1<\/jats:italic>\u2010SMA and COLI expression were weaken by silencing NOX4. In conclusion, FA had potential in anti\u2010hepatic fibrosis at least in part by remolding of extracellular matrix and improving oxidation imbalances to inhibit the activation of HSCs and promote HSCs apoptosis.<\/jats:p>","DOI":"10.1155\/2022\/9938392","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T04:50:06Z","timestamp":1641444606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Forsythiaside A Regulates Activation of Hepatic Stellate Cells by Inhibiting NOX4\u2010Dependent 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