Liquiritigenin attenuates alcohol-induced liver inflammation by regulating the SphK1/S1P/SPNS2 signaling pathway

Background: Alcohol-associated hepatitis (AH) is both a chronic and acute condition, representing the most prevalent manifestation of alcohol-associated liver disease (ALD), characterized by high morbidity and mortality rates. Licorice, known for its hepatoprotective properties, has garnered considerable attention in this context. Liquiritigenin (LQ), a prominent flavonoid derived from licorice roots, exhibits a range of pharmacological properties, including anti-inflammatory, antioxidant, and Anticancer effects. This study aims to investigate the potential of LQ to ameliorate AH by exerting anti-inflammatory effects through the sphingolipid pathway.

Methods: This study establishes an animal model of alcohol-associated hepatitis (AH) using C57BL/6 mice, alongside an in vitro model of alcohol-induced injury in HepG2 cells. Histological assessments were performed using H&E staining and oil red O staining. Furthermore, biochemical markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), reduced glutathione (GSH), and various cytokines were analyzed to evaluate characteristics associated with AH and to assess inflammatory damage. Transcriptomic analysis was conducted to identify differentially expressed genes associated with sphingolipid metabolic pathways, and molecular docking techniques were employed to predict the binding affinity of LQ to target proteins.

Results: LQ can ameliorate liver injury and inflammatory response in AH. Meanwhile, LQ has been shown to inhibit the expression of the sphingolipid signaling pathway in both in vivo and in vitro experiments. Blocking the SphK1/S1P/SPNS2 signaling pathway can effectively alleviate AH. This study provides important theoretical evidence for the hepatoprotective mechanism of LQ and also offers experimental data support for the development of new therapies for AH.

Conclusions: LQ can inhibit the inflammatory response via the SphK1/S1P/SPNS2 pathway, thereby improving AH. This finding provides a molecular basis for its application in the treatment of AH.

Alcohol-associated hepatitis; Liquiritigenin; SphK1/S1P/SPNS2 signaling pathway; Sphingolipid metabolism.