Dietary Supplementation of Auraptene, a Major Component in Citrus reticulata Blanco, Prevents Acute Liver Injury Associated with Apoptosis and Inflammation

Abstract

Auraptene (AP), a coumarin derivative abundant in citrus peels, exhibits diverse bioactivities; however, its role in acute liver injury and the underlying mechanisms remain elusive. This study investigates the hepatoprotective effects of AP against carbon tetrachloride (CCl4)-induced acute liver injury in mice and explored its mechanistic basis. In vitro, transforming growth factor-beta (TGF-β) was employed to stimulate AML-12 hepatocytes to model the injury microenvironment. The impact of AP on the toll-like receptor 2 (TLR2) signaling pathway was assessed through a combination of siRNA gene silencing and signal pathway inhibitors. AP pretreatment significantly decreased the expression of liver injury markers. Additionally, AP can reduce inflammatory (Caspase-1, gasdermin D (GSDMD), interleukin (IL)-1β, IL-18), as well as apoptosis factors (Caspase-3, Caspase-8, P53). Gene silencing experiment confirmed that AP’s anti-inflammatory and antiapoptosis effects depended on the TLR2 signaling pathway. These findings indicate that AP, a food-derived bioactive compound from citrus fruits, effectively mitigates CCl4-provoked acute hepatic injury.