基于网络药理学探讨银屑灵多成分多靶点的整合调节机制

The Yinxieling formula is the conventional drug for psoriasis in Guangdong Provincial Hospital of traditional Chinese medicine. A number of clinical and basic studies showed that Yinxieling formula could effectively improve the symptoms of patients with psoriasis. It had unique advantages of drugs dosage reduction and recurrence prevetion. It adjusted multiple pathological pathways of psoriasis. We already found five chemical components such as isofraxidin can be absorbed into the bloodstream after oral administration of Yinxieling formula. Their molecular targets were also predicted. But the multi-component and multi-target integration adjustment mechanism of Yinxieling formula is still not well clear until now. We need apply new research methods. Network pharmacological methods provide new ideas and means for researchers. Based on our previous work, we plan to apply virtual screening technology to screening of active compounds and the target proteins of Yinxieling formula rapidly. Then we will build and analysis the active compounds-target proteins complex network of Yinxieling formula to identify the key nodes. The binding capacity of active compounds and the target proteins will be measured by biological affinity chromatography. Finally, the in vitro activity of compunds with high affinity will be tested at celluar level. At last, We will reform a new formula with active compounds. The overall effcicacy of new formula will validated by animal model. The multi-component, multi-target, multi-pathway molecular mechanisms of Yinxieling formula were illustrated by modern technology.

银屑灵是本院常用院内制剂，临床和基础研究显示：银屑灵能干预银屑病的多个病理环节，有效改善银屑病患者症状，具有减少西药用量和延缓复发的优势。课题组前期研究发现银屑灵中异嗪皮啶等5种化学成分可吸收入血，并预测了它们的分子靶点。但银屑灵的有效成分群是如何作用于体内靶点群，从而发挥整合调节作用尚不清楚。网络药理学方法对复杂系统具有强大的预测和分析能力，这为我们提供了新的解决手段。本研究拟采用其计算机虚拟技术快速筛选银屑灵的有效成分群、靶点群，进而构建银屑灵的有效成分群与靶点群相互作用复杂网络，通过对网络的分析，明确有效成分群和靶点群之间的关系，随后利用生物亲和色谱技术逐一测定各有效成分与靶点的亲和力，选取亲和力高的有效成分开展活性研究，将有明显活性的成分群重新组成新的复方，最后，通过动物模型验证复方的整体药效，从而实现由天然药物组方向有效成分群组方的转化，为新型中药复方的研究提供了广阔的前景。

银屑灵是我院名老中医禤国维教授针对银屑病核心病机长期凝练形成并经多年临床实践证实疗效确切的经验方，1998年正式获得医院制剂批准文号（粤Z20080123），成为广东省中医院治疗银屑病的常规药物。为深入理解该方的物质基础和作用机制，课题组在国家自然基金的资助下开展了为期一年的探索，取得一批十分有价值的研究成果，目前已经发表国内核心期刊3篇（SCI收录1篇），接收1篇，投稿国外SCI期刊2篇，获得国家版权著作权1项，培养博士后1名，博士生1名，圆满完成项目既定目标，课题组希望能继续得到国家自然基金的资助，开展更加深入的研究，以便透彻地阐释银屑灵组方的科学内涵。