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

作者全名：Zhang, Lidan; Kuang, Ge; Gong, Xia; Huang, Rui; Zhao, Zizuo; Li, Yan; Wan, Jingyuan; Wang, Bin

作者地址：[Zhang, Lidan; Huang, Rui; Zhao, Zizuo; Li, Yan; Wang, Bin] Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Chongqing 400016, Peoples R China; [Kuang, Ge; Wan, Jingyuan] Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Gong, Xia] Chongqing Med Univ, Dept Anat, Chongqing 400016, Peoples R China; [Huang, Rui] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Anesthesiol, Hangzhou 310058, Zhejiang, Peoples R China

通信作者：Wang, B (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Chongqing 400016, Peoples R China.; Wan, JY (通讯作者)，Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China.

来源：TRANSPLANT IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001214074200001

JCR分区：Q3

影响因子：1.6

年份：2024

卷号：84

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Piperine; Hepatic ischemia/reperfusion injury; Inflammation; TLR4; NF-kappa B

摘要：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-kappa B), interleukin-1 receptorassociated 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-alpha) and interleukin 6 (IL-6) production and reduced TLR4 activation and phosphorylation of IRAK1, p38, and NF-kappa B in HIRI. Piperine has a protective effect against HIRI through the TLR4/IRAK1/NF-kappa B signaling pathway and may be a safer option for future clinical treatment and prevention of ischemia-related diseases.

基金机构：National Natural Science Foundation of China [82070714]

基金资助正文：<BOLD>Funding</BOLD> This work was financially supported by the National Natural Science Foundation of China (grant no. 82070714) .