Wu Xiafei, Zhang Feng, Xiong Xin, Lu Chunfeng, Lian Naqi, Lu Yin, Zheng Shizhong
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.
IUBMB Life. 2015 Apr;67(4):312-21. doi: 10.1002/iub.1348. Epub 2015 Apr 3.
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.
肝纤维化与肝脏炎症相伴，而肝脏炎症已被视为慢性肝病的重要治疗靶点。我们之前证明，川芎的有效成分川芎嗪（TMP）可抑制肝星状细胞（HSCs）的活化，从而起到抗肝纤维化的作用。在本研究中，我们的工作表明，TMP改善了大鼠纤维化肝脏的组织学结构，降低了肝酶水平，并减轻了胶原沉积。此外，TMP通过降低包括肿瘤坏死因子-α（TNF-α）、NLRP3、核因子-κB（NF-κB）和白细胞介素-1β（IL-1β）在内的炎症细胞因子水平来抑制炎症，从而显著保护肝脏免受四氯化碳所致的损伤和纤维化。体外实验表明，TMP通过破坏血小板衍生生长因子-β受体（PDGF-βR）/NLRP3/半胱天冬酶1途径抑制HSCs中炎症细胞因子的表达。这些数据共同表明，TMP可减轻肝纤维化中的肝脏炎症，可能是通过PDGF-βR/NLRP3/半胱天冬酶1途径靶向HSCs。这为TMP作为肝纤维化潜在治疗药物提供了新的机制见解。
