Liu Jianling, Sun Ke, Zheng Chunli, Chen Xuetong, Zhang Wenjuan, Wang Zhengzhong, Shar Piar Ali, Xiao Wei, Wang Yonghua
College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China.
College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China; College of Life Science, Northwest A & F University, Yangling, Shaanxi, 712100, China; Center of Bioinformatics, Northwest A & F University, Yangling, Shaanxi, 712100, China.
PLoS One. 2015 Apr 1;10(4):e0123109. doi: 10.1371/journal.pone.0123109. eCollection 2015.
As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.
作为药物发现的丰富自然资源，中药在补充和替代医学体系中发挥着重要作用。中药显示出令人畏惧的化合物复杂性，其具有多成分和多靶点来治疗疾病，因此，使用常规方法充分系统地解释分子机制总是极其困难。在目前的工作中，为了揭示中药复方的系统机制，我们通过整合途径、靶点选择、反向药物靶向和网络分析相结合的方式，开发了一种基于途径的策略，然后以临床广泛使用的中药注射剂热毒宁注射液（RDN）为例，研究其抗炎作用。系统地研究了RDN主要成分在信号通路水平上发挥的抗炎作用。更重要的是，我们的预测结果也得到了实验验证。我们的策略从分子到系统水平提供了对中药复方药理功能的深入理解，这可能会使系统药理学在药物发现和开发中得到更成功的应用。
