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Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP 3 inflammasome pathway
Author(s) -
Wu Xiafei,
Zhang Feng,
Xiong Xin,
Lu Chunfeng,
Lian Naqi,
Lu Yin,
Zheng Shizhong
Publication year - 2015
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1348
Subject(s) - tetramethylpyrazine , hepatic stellate cell , inflammasome , inflammation , fibrosis , cytokine , cancer research , liver injury , tumor necrosis factor alpha , platelet derived growth factor receptor , hepatic fibrosis , chemistry , medicine , pharmacology , growth factor , immunology , receptor , pathology , alternative medicine
Hepatic fibrosis is concomitant with liver inflammation, which has been highlighted as significant treatment of chronic liver disease. We previously demonstrated that tetramethylpyrazine (TMP), the effective component of Ligusticum chuanxiong Hort, can inhibit the activation of HSCs and consequential anti‐hepatic fibrosis. In this study, our work demonstrated that TMP improved liver histological architecture, decreased hepatic enzyme levels and attenuated collagen deposition in the rat fibrotic liver. In addition, TMP significantly protected the liver from CCl4‐caused injury and fibrogenesis by suppressing inflammation with reducing levels of inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), NLRP3, nuclear factor‐kappa B (NF‐κB) and interleukin‐1β (IL‐1β). Experiments in vitro showed that TMP inhibited inflammatory cytokine expression in HSCs associated with disrupting platelet‐derived growth factor‐b receptor (PDGF‐βR)/NLRP3/caspase1 pathway. These data collectively indicate that TMP can attenuate liver inflammation in liver fibrosis and possibly by targeting HSCs via PDGF‐βR/NLRP3/caspase1 pathway. It provides novel mechanistic insights into TMP as a potential therapeutic remedy for hepatic fibrosis. © 2015 IUBMB Life, 67(4):312–321, 2015