title: Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca(2+) overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats.
abstract: Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca(2+) overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca(2+) overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.|Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.|Modern Research Center for Traditional Chinese Medicine of Shanxi University, NO. 92, Wucheng Road, Taiyuan 030006, Shanxi, P. R. China.
authors.forename: Yue-Tao
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.|Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.|Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Jia
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.|Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Chang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.|Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.
authors.forename: Zhong-Mei
authors.initials: ZM
authors.lastname: Zou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D008516:Medicine, Chinese Traditional; D055432:Metabolomics; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D007545:Isoproterenol; D002118:Calcium