Lonicera japonica Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Mice: Molecular Mechanisms of Action
Lonicera japonica Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Mice: Molecular Mechanisms of Action
复制标题
金银花减轻四氯化碳诱导的小鼠肝纤维化：作用的分子机制
DOI：
10.1142/s0192415x19500174
复制
发表时间：
2019-01-01
影响因子：
5.7
通讯作者：
Ji, Lili
中科院分区：
文献类型：
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作者：
Miao, Hui;Zhang, Yi;Ji, Lili
肝纤维化是一个世界性的临床问题，通常会导致肝硬化。金银花（Lonicera japonica Thunb）的干燥花蕾，是我国传统的清热解毒中药。本研究旨在观察金银花（FL）水提取物对四氯化碳（CCl4）诱导的小鼠肝纤维化的保护作用。通过腹腔注射2ml/kg CCl4，每周两次，持续4周，诱导小鼠肝纤维化。 Masson三色和天狼星红染色结果、肝脏羟脯氨酸含量和血清IV胶原蛋白含量证明FL对CCl4诱导的小鼠肝纤维化有减弱作用。在用 CCl4 治疗的小鼠中，FL 减少了肝星状细胞 (HSC) 的活化并逆转了上皮间质转化 (EMT) 过程。 FL 还可以减轻 CCl4 治疗小鼠的肝脏氧化应激损伤，并增强核因子红细胞 2 相关因子 2 (Nrf2) 抗氧化信号通路的激活。此外，FL 中的主要酚酸，包括绿原酸 (CGA) 和咖啡酸 (CA)，在体外都能减少 HSC 活化。总之，FL 通过抑制 HSC 活化、逆转 EMT 并通过诱导 Nrf2 活化减少肝脏氧化应激损伤来减轻 CCl4 诱导的小鼠肝纤维化。 CGA 可能是 FL 抗纤维化活性的主要活性化合物。
Liver fibrosis is a worldwide clinical issue that generally causes hepatic cirrhosis. Lonicerae Japonicae Flos (dried flower buds of Lonicera japonica Thunb) is a traditional heat-clearing and detoxifying herbal medicine in China. This study aims to observe the protection of the water extract of Lonicerae Japonicae Flos (FL) from carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2 ml/kg CCl4 twice a week for 4 weeks. FL's attenuation of CCl4-induced liver fibrosis in mice was evidenced by the results of Masson's trichrome and Sirius red staining, liver hydroxyproline content and serum amount of collagen IV. FL reduced hepatic stellate cells (HSCs) activation and reversed the epithelial-mesenchymal transition (EMT) process in mice treated with CCl4. FL also alleviated liver oxidative stress injury and enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) anti-oxidant signaling pathway in mice treated with CCl4. Additionally, the main phenolic acids in FL including chlorogenic acid (CGA) and caffeic acid (CA) both reduced HSCs activation in vitro. In summary, FL attenuates CCl4-induced liver fibrosis in mice by inhibiting HSCs activation, reversing EMT and reducing liver oxidative stress injury via inducing Nrf2 activation. CGA may be the main active compound contributing to the antifibrotic activity of FL.