Piperine attenuates hepatic ischemia/reperfusion injury via suppressing the TLR4 signaling cascade in mice

Lidan Zhang; Ge Kuang; Xia Gong; Rui Huang; Zizuo Zhao; Yan Li; Jingyuan Wan; Bin Wang

doi:10.1016/j.trim.2024.102033

Piperine attenuates hepatic ischemia/reperfusion injury via suppressing the TLR4 signaling cascade in mice

Transpl Immunol. 2024 Mar 13:84:102033. doi: 10.1016/j.trim.2024.102033. Online ahead of print.

Authors

Lidan Zhang¹, Ge Kuang², Xia Gong³, Rui Huang⁴, Zizuo Zhao¹, Yan Li¹, Jingyuan Wan⁵, Bin Wang⁶

Affiliations

¹ Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
² Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
³ Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
⁴ Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang 310058, China.
⁵ Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: jywan@cqmu.edu.cn.
⁶ Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: wb@hosipital.cqmu.edu.cn.

PMID: 38484898
DOI: 10.1016/j.trim.2024.102033

Abstract

Piperine, the major active substance in black pepper, has been shown to have anti-inflammatory and antioxidant effects in several ischemic diseases. However, the role of piperine in hepatic ischemia/reperfusion injury (HIRI) and its underlying mechanisms remain unclear. In this study, the mice were administered piperine (30 mg/kg) intragastric administration before surgery. After 24 h of hepatic ischemia-reperfusion, liver histopathological evaluation, serum transaminase measurements, and TUNEL analysis were performed. The infiltration of inflammatory cells and production of inflammatory mediators in the liver tissue were determined by immunofluorescence and immunohistochemical staining. The protein levels of toll-like receptor 4 (TLR4) and related proteins such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-1 receptor-associated kinase 1 (IRAK1), p65, and p38 were detected by western blotting. The results showed that plasma aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte apoptosis, oxidative stress, and inflammatory cell infiltration significantly increased in HIRI mice. Piperine pretreatment notably repaired liver function, improved the histopathology and apoptosis of liver cells, alleviated oxidative stress injury, and reduced inflammatory cell infiltration. Further analysis showed that piperine attenuated tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) production and reduced TLR4 activation and phosphorylation of IRAK1, p38, and NF-κB in HIRI. Piperine has a protective effect against HIRI through the TLR4/IRAK1/NF-κB signaling pathway and may be a safer option for future clinical treatment and prevention of ischemia-related diseases.

Keywords: Hepatic ischemia/reperfusion injury; Inflammation; NF-κB; Piperine; TLR4.