Geng Yan, Sun Qing, Li Wang, Lu Zhen-Ming, Xu Hong-Yu, Shi Jin-Song, Xu Zheng-Hong
School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu, China.
Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
Mol Nutr Food Res. 2017 Apr;61(4). doi: 10.1002/mnfr.201600392. Epub 2017 Feb 6.
Myricetin is found in most berries, vegetables, and various medicinal herbs, which has been reported to possess various bio-activities. However, the role of myricetin on liver fibrosis remains to be elucidated.
Hepatic stellate cell (HSC) line CFSC-8B was stimulated by transforming growth factor β1 (TGF-β1) or platelet-derived growth factor BB (PDGF-BB) to induce liver fibrosis in vitro. The results showed that myricetin significantly ameliorated TGF-β1- or PDGF-BB-induced HSCs activation, cell migration, and extracellular matrix production; blocked TGF-β1-induced phosphorylation of Smad2, P38, extracellular signal-regulated kinase (ERK), and protein kinase B (Akt); and downregulated PDGF-BB stimulated phosphorylation of extracellular signal-regulated kinase and Akt in HSCs in a dose-dependent manner. Meanwhile, the carbon tetrachloride (CCl ) induced mouse model has been used to study antifibrosis role of myricetin in vivo. Our data demonstrated that myricetin suppressed α-smooth muscle actin and collagen type I deposition and blocked phosphorylation of Smad2, mitogen-activated protein kinases, and Akt in CCl -treated mice.
Myricetin inhibits the activation of HSCs and ameliorates CCl -induced liver fibrosis in mice and may serve as a potential therapeutic agent in the treatment of liver fibrosis.
杨梅素存在于大多数浆果、蔬菜和各种药草中，据报道具有多种生物活性。然而，杨梅素在肝纤维化中的作用仍有待阐明。
用转化生长因子β1（TGF-β1）或血小板衍生生长因子BB（PDGF-BB）刺激肝星状细胞（HSC）系CFSC-8B，在体外诱导肝纤维化。结果表明，杨梅素显著改善了TGF-β1或PDGF-BB诱导的肝星状细胞激活、细胞迁移和细胞外基质产生；阻断了TGF-β1诱导的Smad2、P38、细胞外信号调节激酶（ERK）和蛋白激酶B（Akt）的磷酸化；并以剂量依赖性方式下调了PDGF-BB刺激的肝星状细胞中细胞外信号调节激酶和Akt的磷酸化。同时，利用四氯化碳（CCl₄）诱导的小鼠模型研究了杨梅素在体内的抗纤维化作用。我们的数据表明，杨梅素抑制了α平滑肌肌动蛋白和I型胶原蛋白的沉积，并阻断了CCl₄处理小鼠中Smad2、丝裂原活化蛋白激酶和Akt的磷酸化。
杨梅素抑制肝星状细胞的激活，改善CCl₄诱导的小鼠肝纤维化，可能作为治疗肝纤维化的潜在治疗剂。
