Piceatannol alleviates liver ischaemia/reperfusion injury by inhibiting TLR4/NF-κB/NLRP3 in hepatic macrophages

Background: Macrophages present strong immunomodulatory ability and are considered to be core immune cells in the process of hepatic ischaemia-reperfusion (I/R). The NLRP3 inflammasome is a kind of intracellular multimolecular complex that actively participates in innate immune responses and proinflammatory signalling pathways. Piceatannol (PIC) is a derivative of the natural phenolic compound resveratrol and has antioxidant and anti-inflammatory effects. The purpose of this study was to examine whether pretreatment with PIC can alleviate hepatic I/R injury by targeting NLRP3 inflammasome-induced macrophage pyroptosis.Methods: PIC-pretreated primary hepatic macrophages were subjected to hypoxia/reoxygenation, and liver ischaemia/reperfusion was performed in mice.Results: PIC pretreatment ameliorated histopathological changes, oxidative stress and inflammation while enhancing antioxidant and anti-inflammasome markers through downregulation of Toll-like receptor 4 (TLR4), p-I kappa B alpha (S32), p-NF-kappa Bp65 (S536), NLRP3, caspase-1 (p20), IL-18, IL-18 and GSDMD-N expression during liver ischaemia-reperfusion. Moreover, PIC inhibited the translocation of NF-kappa B p65 after stimulation with hypoxia/ reoxygenation in primary hepatic macrophages.Conclusions: The results indicated that PIC protected the liver against hepatic I/R injury, which was mediated by targeting TLR4-NF-kappa B-NLRP3-mediated hepatic macrophage pyroptosis.

Automated summary

This study demonstrates that pretreatment with PIC can alleviate hepatic ischemia-reperfusion (I/R) injury by targeting the TLR4-NF-kappa B-NLRP3 pathway. PIC reduces histopathological changes, oxidative stress, and inflammation, while enhancing antioxidant and anti-inflammatory markers by downregulating the expression of TLR4, p-I kappa B alpha (S32), p-NF-kappa Bp65 (S536), NLRP3, caspase-1 (p20), IL-18, IL-18, and GSDMD-N. Moreover, PIC inhibits the translocation of NF-kappa B p65 after hypoxia/reoxygenation stimulation.