Forsythoside A Alleviates Acute Alcoholic Liver Injury by Binding to TLR4 to Inhibit the Activation of the NF‐κB Pathway

ABSTRACT Forsythoside A (FTA) is a key component found in the fruit and leaves of Forsythia suspensa , having anti‐inflammatory and antioxidant properties. However, it is unclear whether FTA can have a protective effect against acute alcoholic liver injury (ALI) and how it may exert this effect. This research examined the potential protective effects of FTA against acute ALI using cell and animal models. The protective properties of FTA against acute ALI were attributed to its anti‐inflammatory and antioxidant actions by detecting the markers of oxidative stress and inflammation. The underlying mechanism was explored through the utilization of Western blotting, Molecular Docking, and Microscale Thermophoresis techniques. The results showed that pretreatment with high doses of FTA had a significant protective effect on acute ALI in both cell and animal models. The pretreatment with high doses of FTA inhibited alcohol‐induced oxidative stress and inflammation, raising antioxidative enzyme activity in both models. Furthermore, FTA has been shown to bind to TLR4, thereby inhibiting alcohol‐induced activation of the NF‐κB signaling pathway, leading to a decrease in cellular oxidative stress and inflammatory reactions. This interaction also facilitates the ubiquitination‐mediated degradation of TLR4, ultimately diminishing its regulatory impact on the NF‐κB signaling cascade. FTA has a significant protective effect on acute ALI. It binds to TLR4 to inhibit the activation of the NF‐κB signaling pathway by alcohol, thereby reducing oxidative stress and inflammation and exerting a protective effect. The results of our study provide a theoretical basis for the development of FTA for the prevention and treatment of acute ALI.