Atractylodin attenuated hepatic ischemia reperfusion injury in mice by regulating TLR4-NLRP3-ASC signal pathway

Background: Hepatic ischemia-reperfusion injury (IRI), as the critical condition commonly related to shock or liver surgery, often results in extensive tissue damage and impairs liver function. Atractylodin (ATR), the main bioactive compound obtained from the Atractylodes rhizome, exhibits anti-inflammatory, antioxidant, and cytoprotective properties. Nonetheless, its effects on hepatic IRI and its associated mechanisms are largely unclear. Methods: In the present work, ATR (40 mg/kg) was administered via gavage every 12 h for 3 days prior to the induction of IRI. Meanwhile, liver function, histopathology, pyroptosis markers, oxidative stress, and inflammatory cytokine levels were assessed. Result: The results revealed that ATR pretreatment significantly improved liver function and histopathological outcomes, while reducing transaminase activity, apoptosis, inflammatory cytokine levels, and oxidative stress. Furthermore, ATR inhibited the activation of TLR4 and NOD-like receptor protein 3 (NLRP3) inflammasomes, including the NLRP3 and ASC protein, thereby attenuating downstream inflammatory factor production and maturation and reducing pyroptosis. Conclusions: ATR protects against hepatic IRI through regulating the TLR4-NLRP3-ASC signaling pathway, highlighting its potential clinical utility.