title: Entropy-based divergent and convergent modular pattern reveals additive and synergistic anticerebral ischemia mechanisms.
abstract: Module-based network analysis of diverse pharmacological mechanisms is critical to systematically understand combination therapies and disease outcomes. We first constructed drug-target ischemic networks in baicalin, jasminoidin, ursodeoxycholic acid, and their combinations baicalin and jasminoidin as well as jasminoidin and ursodeoxycholic acid groups and identified modules using the entropy-based clustering algorithm. The modules 11, 7, 4, 8 and 3 were identified as baicalin, jasminoidin, ursodeoxycholic acid, baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid-emerged responsive modules, while 12, 8, 15, 17 and 9 were identified as disappeared responsive modules based on variation of topological similarity, respectively. No overlapping differential biological processes were enriched between baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid pure emerged responsive modules, but two were enriched by their co-disappeared responsive modules including nucleotide-excision repair and epithelial structure maintenance. We found an additive effect of baicalin and jasminoidin in a divergent pattern and a synergistic effect of jasminoidin and ursodeoxycholic acid in a convergent pattern on "central hit strategy" of regulating inflammation against cerebral ischemia. The proposed module-based approach may provide us a holistic view to understand multiple pharmacological mechanisms associated with differential phenotypes from the standpoint of modular pharmacology.
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: 2 Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Li
authors.affiliation: 2 Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Yinying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Pengqian
authors.initials: P
authors.lastname: Wang
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Kang
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Wu
authors.affiliation: 1 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei, Beijing 100700, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D019277:Entropy; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use; D063990:Gene Ontology; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D039823:Iridoids / Q000008:administration & dosage / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D059467:Transcriptome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D005419:Flavonoids; D039823:Iridoids; D018696:Neuroprotective Agents; C007835:geniposide; C038044:baicalin; D014580:Ursodeoxycholic Acid
keywords: Modular pharmacology; additive effect; cerebral ischemia; disappeared responsive module; emerged responsive module; synergistic effect