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

  • Eur J Pharmacol. 2023 Oct 20:176149. doi: 10.1016/j.ejphar.2023.176149.
Lei Yao  1 ,  Haijian Cai  2 ,  Qi Fang  3 ,  Deng Liu  3 ,  Mengting Zhan  3 ,  Lijian Chen  4 ,  Jian Du  5
Affiliations
  • 1. Department of Biochemistry and Molecular Biology, Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China; Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Anhui Medical University, Hefei, 230032, China.
  • 2. Center for Scientific Research of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
  • 3. Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
  • 4. Center for Scientific Research of Anhui Medical University, Anhui Medical University, Hefei, 230032, China. Electronic address: [email protected].
  • 5. Department of Biochemistry and Molecular Biology, Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China; Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Anhui Medical University, Hefei, 230032, China; Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. Electronic address: [email protected].
PMID: 37866744 DOI: 10.1016/j.ejphar.2023.176149
Abstract

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-IκBα (S32), p-NF-κBp65 (S536), NLRP3, Caspase-1 (p20), IL-1β, IL-18 and GSDMD-N expression during liver ischaemia‒reperfusion. Moreover, PIC inhibited the translocation of NF-κB 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-κB-NLRP3-mediated hepatic macrophage Pyroptosis.

Keywords
Hepatic macrophages; Inflammation; Liver ischemia/reperfusion; NLRP3; Piceatannol.
Products