In the peel of citrus (Rutaceae) fruit, hesperitin (Hesp), a flavanone glycoside chemical, is found naturally. Hesp has been found to have a wide range of pharmacological actions, including anti-inflammatory, antioxidant, antiviral, and anticancer properties, according to earlier research. However, nothing is known regarding its function in alcoholic liver steatosis and inflammation. In this study, we employed a network pharmacology approach to identify the TLR4 signaling pathway as a primary target of Hesp for the treatment of alcoholic steatohepatitis (ASH). Molecular docking results showed that Hesp bound to the representative target TLR4 and exhibited good affinity. In addition, Hesp inhibits the TLR4 target and consequently the NF-κB signaling pathway, which in turn slows the evolution of alcoholic steatohepatitis, according to further in vitro and in vivo tests. The results of this study preliminarily indicate that Hesp is an ideal drug candidate for the treatment of ASH.
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