title: Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway.
abstract: 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.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Xiafei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.|National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Naqi
authors.initials: N
authors.lastname: Lian
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.|National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.|National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D010982:Platelet-Derived Growth Factor; D011719:Pyrazines; D020170:Caspase 1; C017953:tetramethylpyrazine
keywords: NLRP3 inflammasome; hepatic stellate cells; inflammation; liver fibrosis; tetramethylpyrazine