基于片段搜索和相似性搜索的抗哮喘中药发现研究

Fragment and Similarity based on Virtual Screening for Anti-asthma Traditional Chinese Medicine

目的:探讨利用防治哮喘的常用化学药物结构信息筛选活性中药。方法:以Drugbank数据库中具有明确治疗哮喘的活性化学药物为基础,以活性片段搜索和结构相似性搜索为筛选方法,获得具有防治哮喘的中药成分;追溯活性成分的来源中药,并结合中医防治哮喘的治法治则,探讨进行组方。结果:以36个作用于8个靶点的化学药物为基础,通过活性片段搜索获得62个药效成分,相似性搜索获得10个药效成分,总计72个药效成分来自39个常用中药,包括麻黄、半夏、细辛、生姜、地龙、甘草、麦冬、紫菀和吴茱萸等已被证明具有抗哮喘作用的中药;结合热哮清热宣肺,化痰降逆;寒哮温肺散寒,化痰平喘的中医治法治则,分别探讨组合了麻黄、半夏、生姜、甘草和麻黄、地龙、甘草两个作用于多靶点整体治疗的方剂。结论:应用片段搜索和相似性搜索的方法进行中药的发现研究具有一定的可行性。

Objective： To obtain new potential active traditional Chinese medicine（TCM） compounds for the prevention and treatment of asthma.Method： The drugs with anti-asthma activity were collected from Drugbank database.Two virtual screening methods,active fragment-based and structural similarity-based,were used respectively for the screening of potential active TCM compounds from traditional Chinse medicine database（TCMD 2009）.Combined the principles and methods of TCM,the source TCM of the hit compounds were then traced for the formulating prescription against asthma.Result： Thirty-six drugs with the action on eight targets were obtained from the Drugbank database.Seventy-two potential active compounds,which come from 39 commonly used TCM,were hit by virtual screening.Some of the source TCM have been demonstrated to have the anti-asthma effect,such as ephedra,pinellia,asarum,ginger,earthworm,licorice,ophiopogon,aster,evodia and so on.The principle of clearing lung-heat and removing phlegm for lowering adverse qi is always used for the treatment of thermal asthma,while the warming lung for dispelling cold and removing phlegm is for cold asthma.Two prescriptions were discussed for thermal and cold asthma respectively.The prescription consisted by ephedra,pinellia,ginger,licorice was discussed for cold asthma,while the prescription of ephedra,earthworm,licorice for thermal asthma.Conclusion： The results showed that the application of fragment-based search and similarity search methods are feasible for the discovery of Chinese medicine.