title: Systems pharmacology to decipher the combinational anti-migraine effects of Tianshu formula.
abstract: Migraine is the most common neurovascular disorder that imparts a considerable burden to health care system around the world. However, currently there are still no effective and widely applicable pharmacotherapies for migraine patients. Herbal formulae, characterized as multiple herbs, constituents and targets, have been acknowledged with clinical effects in treating migraine, which attract more and more researchers' attention although their exact molecular mechanisms are still unclear. In this work, a novel systems pharmacology-based method which integrates pharmacokinetic filtering, target fishing and network analysis was developed and exemplified by a probe, i.e. Tianshu formula, a widely clinically used anti-migraine herbal formula in China which comprises of Rhizoma chuanxiong and Gastrodia elata. The results exhibit that 20 active ingredients of Tianshu formula possess favorable pharmacokinetic profiles, which have interactions with 48 migraine-related targets to provide potential synergistic therapeutic effects. Additionally, from systematic analysis, we speculate that R. chuanxiong as the monarch herb mediates the major targets like PTGS2, ESR1, NOS2, HTR1B and NOS3 to regulate the vascular and nervous systems, as well as the inflammation and pain-related pathways to benefit migraine patients. Meanwhile, as an adjuvant herb, G. elata may not only assist the monarch herb to improve the outcome of migraine patients, but also regulate multiple targets like ABAT, HTR1D, ALOX15 and KCND3 to modify migraine accompanying symptoms like vomiting, vertigo and gastrointestinal disorders.
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China. Electronic address: yanli@dlut.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China; School of Chemistry and Environmental Engineering, Hubei University for Nationalities, Enshi, Hubei 445000, China.
authors.forename: Jingxiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Environmental Engineering, Hubei University for Nationalities, Enshi, Hubei 445000, China.
authors.forename: Lilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Xuetong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Computer Information Science and Engineering, University of Florida, Gainesville, FL 32608, USA.
authors.forename: Su-Shing
authors.initials: SS
authors.lastname: Chen
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu 222001, PR China. Electronic address: kanionlunwen@163.com.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu 222001, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Lab of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address: yh_wang@nwsuaf.edu.cn.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
mesh_terms: D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D008881:Migraine Disorders / Q000175:diagnosis / Q000188:drug therapy*; D049490:Systems Biology / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal
keywords: Migraine; Pharmacokinetics; Systems pharmacology; Tianshu formula