title: Variation of pathways and network profiles reveals the differential pharmacological mechanisms of each effective component to treat middle cerebral artery ischemia-reperfusion mice.
abstract: Using a system pharmacology strategy, this study evaluated the unique pharmacological characteristics of three different neuroprotective compounds for the treatment of cerebral ischemia-reperfusion. A microarray including 374 brain ischemia-related genes was used to identify the differentially expressed genes among five treatment groups: baicalin, jasminoidin, ursodeoxycholic acid, sham, and vehicle, and MetaCore analysis software was applied to identify the significantly altered pathways, processes and interaction network parameters. At pathway level, 46, 25, and 31 pathways were activated in the baicalin, jasminoidin, and ursodeoxycholic acid groups, respectively. Thirteen pathways mainly related with apoptosis and development were commonly altered in the three groups. Additionally, baicalin also targeted pathways related with development, neurophysiologic process and cytoskeleton remodeling, while jasminoidin targeted pathways related with cell cycle and ursodeoxycholic acid targeted those related with apoptosis and development. At process level, three processes were commonly regulated by the three groups in the top 10 processes. Further interaction network analysis revealed that baicalin, jasminoidin, and ursodeoxycholic acid displayed unique features either on network topological parameters or network structure. Additional overlapping analysis demonstrated that compared with ursodeoxycholic acid, the pharmacological mechanism of baicalin was more similar with that of jasminoidin in treating brain ischemia. The data presented in this study may contribute toward the understanding of the common and differential pharmacological mechanisms of these three compounds.
authors.affiliation: China Academy of Chinese Medical Sciences, Beijing 100700, China Shanxi Buchang Pharmaceutical Co., Ltd, Shaanxi 710075.
authors.forename: HaiXia
authors.initials: H
authors.lastname: Dang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: KangNing
authors.initials: K
authors.lastname: Li
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: YaNan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: YingYing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: PengQian
authors.initials: P
authors.lastname: Wang
authors.affiliation: Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: China Food and Drug Administration, Beijing 100053, China.
authors.forename: HaiNan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China zhonw@sina.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: YongYan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D039823:Iridoids / Q000008:administration & dosage / Q000494:pharmacology; D007511:Ischemia; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D046228:Microarray Analysis; D020768:Middle Cerebral Artery; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D039823:Iridoids; D018696:Neuroprotective Agents; C007835:geniposide; C038044:baicalin; D014580:Ursodeoxycholic Acid
keywords: Systems pharmacology; baicalin; brain ischemia; jasminoidin; ursodeoxycholic acid