Liu Xiujie, Shi Yu, Hu Yinghui, Luo Ke, Guo Ying, Meng Weiwei, Deng Yulin, Dai Rongji
School of Life Science, Institute of Space Biology and Medical Engineering, Beijing Institute of Technology, Beijing, China.
School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China.
Front Pharmacol. 2018 May 17;9:524. doi: 10.3389/fphar.2018.00524. eCollection 2018.
Liver fibrosis is a common pathological feature of many chronic liver diseases. Wall.ex DC (ZYCH) is a promising therapeutic for liver fibrosis. In this study, 25 compounds were isolated from ZYCH, and the effects of ZYCH on DMN-induced liver fibrosis in rats were evaluated. The optimal effect group (H-ZYCH group) was selected for further proteomic analysis, and 282 proteins were altered in comparison to the DMN model group (FC > 1.2 or < 0.83, < 0.05). Based on GO annotation analysis, clusters of drug metabolism, oxidative stress, biomolecular synthesis and metabolism, positive regulation of cell growth, extracellular matrix deposition, and focal adhesion were significantly regulated. Then networks of the altered proteins and compounds was generated by Cytoscape. Importantly, triterpenoid saponins and lignans had possessed high libdock scores, numerous targets, important network positions, and strong inhibitory activity. These findings may suggest that triterpenoid saponins and lignans are important active compounds of ZYCH in liver fibrosis and targeted by proteins involved in liver fibrosis. The combination of network pharmacology with proteomic analysis may provide a forceful tool for exploring the effect mechanism of TCM and identifying bioactive ingredients and their targets.
肝纤维化是许多慢性肝病的常见病理特征。Wall.ex DC（ZYCH）是一种有前景的肝纤维化治疗药物。在本研究中，从ZYCH中分离出25种化合物，并评估了ZYCH对二甲基亚硝胺（DMN）诱导的大鼠肝纤维化的影响。选择最佳效应组（H-ZYCH组）进行进一步的蛋白质组学分析，与DMN模型组相比，有282种蛋白质发生了变化（FC>1.2或<0.83，<0.05）。基于基因本体（GO）注释分析，药物代谢、氧化应激、生物分子合成与代谢、细胞生长的正调控、细胞外基质沉积和粘着斑等簇被显著调控。然后通过Cytoscape生成了改变的蛋白质和化合物的网络。重要的是，三萜皂苷和木脂素具有较高的libdock评分、众多靶点、重要的网络位置和较强的抑制活性。这些发现可能表明，三萜皂苷和木脂素是ZYCH在肝纤维化中的重要活性化合物，并被参与肝纤维化的蛋白质靶向。网络药理学与蛋白质组学分析相结合可能为探索中药的作用机制以及鉴定生物活性成分及其靶点提供有力工具。
