title: Synergism and rules of the new combination drug Yiqijiedu formulae (YQJD) on ischemic stroke based on amino acids (AAs) metabolism.
abstract: The use of combination drugs is considered to be a promising strategy to control complex diseases such as ischemic stroke. The detection of metabolites has been used as a versatile tool to reveal the potential mechanism of diverse diseases. In this study, the levels of 12 endogenous AAs were simultaneously determined quantitatively in the MCAO rat brain using RRLC-QQQ method. Seven AAs were chosen as the potential biomarkers, and using PLS-DA analysis, the effects of the new combination drug YQJD, which is composed of ginsenosides, berberine, and jasminoidin, on those 7 AAs were evaluated. Four AAs, glutamic acid, homocysteine, methionine, and tryptophan, which changed significantly in the YQJD-treated groups compared to the vehicle groups (P < 0.05), were identified and designated as the AAs to use to further explore the synergism of YQJD. The result of a PCA showed that the combination of these three drugs exhibits the strongest synergistic effect compared to other combination groups and that ginsenosides might play a pivotal role, especially when combined with jasminoidin. We successfully explored the synergetic mechanism of multi-component and provided a new method for evaluating the integrated effects of combination drugs in the treatment of complex diseases.
authors.affiliation: 1] Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700 [2] School of Pharmacy, Hebei University, Hebei Baoding 071002 [3].
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: 1] Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700 [2].
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: 1] Beijing University of Chinese Medicine 100029 [2].
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Chen
authors.affiliation: College of life science and engineering, Southwest Jiaotong University, Sichuan Chengdu 610031.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Wen
authors.affiliation: School of Pharmacy, Hebei University, Hebei Baoding 071002.
authors.forename: Geng-Liang
authors.initials: GL
authors.lastname: Yang
authors.affiliation: Beijing University of Chinese Medicine 100029.
authors.forename: Fei-Peng
authors.initials: FP
authors.lastname: Duan
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Jiangsu Nanjing 210009.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Huang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700.
authors.forename: De-Feng
authors.initials: DF
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700.
authors.forename: Ding-Rong
authors.initials: DR
authors.lastname: Yu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: 1] Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700 [2] Beijing University of Chinese Medicine 100029.
authors.forename: Shao-Jing
authors.initials: SJ
authors.lastname: Li
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004338:Drug Combinations; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal