Chang Hao-Teng, Tseng Louis J, Hung Ta-Jen, Kao Blacky T, Lin Wei-Yong, Fan Tan-chi, Chang Margaret Dah-Tsyr, Pai Tun-Wen
Graduate Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan.
BMC Syst Biol. 2010 Sep 13;4 Suppl 2(Suppl 2):S8. doi: 10.1186/1752-0509-4-S2-S8.
The eosinophil cationic protein (ECP) is cytotoxic to bacteria, viruses, parasites and mammalian cells. Cells are damaged via processes of pore formation, permeability alteration and membrane leaking. Some clinical studies indicate that ECP gathers in the bronchial tract of asthma sufferers, damages bronchial and airway epithelial cells, and leads to in breathing tract inflammation; therefore, prevention of the cytotoxicity caused by ECP may serve as an approach to treat airway inflammation. To achieve the purpose, reduction of the ECP-cell interactions is rational. In this work, the Chinese herbal combinative network was generated to predict and identify the functional herbs from the pools of prescriptions. It was useful to select the node herbs and to demonstrate the relative binding ability between ECP and Beas-2B cells with or withour herb treatments.
Eighty three Chinese herbs and prescriptions were tested and five effective herbs and six prescription candidates were selected. On the basis of effective single-herbal drugs and prescriptions, a combinative network was generated. We found that a single herb, Gan-cao, served as a node connecting five prescriptions. In addition, Sheng-di-huang, Dang-guei and Mu-tong also appeared in five, four and three kinds of prescriptions, respectively. The extracts of these three herbs indeed effectively inhibited the interactions between ECP and Beas-2B cells. According to the Chinese herbal combinative network, eight of the effective herbal extracts showed inhibitory effects for ECP internalizing into Beas-2B cells. The major components of Gang-cao and Sheng-di-huang, glycyrrhizic acid and verbascose, respectively, reduced the binding affinity between ECP and cells effectively.
Since these Chinese herbs reduced the binding affinity between ECP and cells and inhibited subsequent ECP entrance into cells, they were potential for mitigating the airway inflammation symptoms. Additionally, we mentioned a new concept to study the Chinese herbs using combinative network in the field of systems biology. The functional single herbs could be identified from the set of prescriptions.
嗜酸性粒细胞阳离子蛋白（ECP）对细菌、病毒、寄生虫和哺乳动物细胞具有细胞毒性。细胞通过孔形成、通透性改变和膜渗漏过程受到损伤。一些临床研究表明，ECP聚集在哮喘患者的支气管中，损伤支气管和气道上皮细胞，并导致呼吸道炎症；因此，预防ECP引起的细胞毒性可能是治疗气道炎症的一种方法。为了实现这一目的，减少ECP与细胞的相互作用是合理的。在这项工作中，构建了中药组合网络以从方剂库中预测和识别具有功能的草药。这对于选择节点草药以及展示有无草药处理时ECP与Beas-2B细胞之间的相对结合能力很有用。
测试了83种中药及其方剂，选择了5种有效草药和6种候选方剂。基于有效的单味草药和方剂，构建了一个组合网络。我们发现单味草药甘草作为连接五个方剂的节点。此外，生地黄、当归和木通也分别出现在五种、四种和三种方剂中。这三种草药的提取物确实有效地抑制了ECP与Beas-2B细胞之间的相互作用。根据中药组合网络，8种有效的草药提取物对ECP内化进入Beas-2B细胞具有抑制作用。甘草和生地黄的主要成分，即甘草酸和棉子糖，分别有效地降低了ECP与细胞之间的结合亲和力。
由于这些中药降低了ECP与细胞之间的结合亲和力并抑制了随后的ECP进入细胞，它们具有减轻气道炎症症状的潜力。此外，我们提出了一个在系统生物学领域中使用组合网络研究中药的新概念。可以从方剂集中识别出具有功能的单味草药。
