基于生物网络调控的方剂研究模式与实践

Framework and practice of network-based studies for Chinese herbal formula

方剂的证候效应及其多靶点作用的科学阐释是目前方剂现代研究的关键问题。我们引入和发展了生物信息学和系统生物学等多学科方法,提出从生物网络调控角度研究方剂原理的框架。并在此基础上阐述方证关系和方剂协同作用机制等研究实例,包括从寒热证候网络构建与模式分析角度探讨方证关系,以血管新生为例构建疾病相关网络,从寒性方剂中提取具有抗血管新生协同作用的中药组合并研究其网络调控机制。研究结果表明,从生物网络的角度可较好地解释方证、病证关系,方剂协同作用的"涌现"可能来自方中多成分在作用靶点上的网络联系。提示基于生物网络及其调控的方剂研究模式,结合"中医药生物信息学"、"中医药计算系统生物学"计算与实验方法,可望为方剂研究开辟新途径。

The ZHENG （syndrome of traditional Chinese medicine） oriented effects and the multiple-targets mechanism are the main challenges encountered by recent researches for Chinese herbal formula. Using methods of bioinformatics and systems biology, we proposed a biological network-based framework for understanding the mechanism of Chinese herbal formula, and reviewed our studies under this framework which aimed to explore the relationship between Chinese herbal formula and corresponding ZHENGs, as well as the synergism of herbal combinations. These studies include the network construction for cold or heat ZHENG and its relationship with herbal formula of hot or cold nature, the biological network construction of angiogenesis, and the network regulation-based emergent property of an herbal combination with anti-angiogenesis synergism extracting from the cold formula. It is shown that the ZHENG-oriented effects and the herbal synergism can be nicely explicated by such network-based approaches. Thus, the network-based drug combination discovery, as well as the “traditional Chinese medicine bioinformatics （TCMB） ”and “TCM computational systems biology” combining with computational and experimental approaches, is conceivable and can open a new avenue for understanding Chinese herbal formula.