title: Multipronged Therapeutic Effects of Chinese Herbal Medicine Qishenyiqi in the Treatment of Acute Myocardial Infarction.
abstract: Background:Based on global gene expression profile, therapeutic effects of Qishenyiqi (QSYQ) on acute myocardial infarction (AMI) were investigated by integrated analysis at multiple levels including gene expression, pathways involved and functional group.Methods:Sprague-Dawley (SD) rats were randomly divided into 3 groups: Sham-operated, AMI model (left anterior descending coronary artery ligation) and QSYQ-treated group. Cardiac tissues were obtained for analysing digital gene expression. Sequencing and transcriptome analyses were performed collaboratively, including analyses of differential gene expression, gene co-expression network, targeted attack on network and functional grouping. In this study, a new strategy known as keystone gene-based group significance analysis was also developed.Results:Analysis of top keystone QSYQ-regulated genes indicated that QSYQ ameliorated ventricular remodeling (VR), which is an irreversible process in the pathophysiology of AMI. At pathway level, both well-known cardiovascular diseases and cardiac signaling pathways were enriched. The most remarkable finding was the novel therapeutic effects identified from functional group analysis. This included anti-inflammatory effects mediated via suppression of arachidonic acid lipoxygenase (LOX) pathway and elevation of nitric oxide (NO); and amelioration of dyslipidaemia mediated via fatty acid oxidation. The regulatory patterns of QSYQ on key genes were confirmed by western blot, immunohistochemistry analysis and measurement of plasma lipids, which further validated the therapeutic effects of QSYQ proposed in this study.Conclusions:QSYQ exerts multipronged therapeutic effects on AMI, by concurrently alleviating VR progression, attenuating inflammation induced by arachidonic acid LOX pathway and NO production; and ameliorating dyslipidaemia.
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical College, Beijing University of Chinese Medicine Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Lin
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine Beijing, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, State University of New York at Buffalo Buffalo, NY, USA.
authors.forename: Sarita
authors.initials: S
authors.lastname: Singhal
authors.affiliation: Niagara Falls Memorial Medical Center and Invision Health Buffalo, NY, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Jain
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, State University of New York at BuffaloBuffalo, NY, USA; Genome, Environment and Microbiome Community of Excellence, State University of New York at BuffaloBuffalo, NY, USA; Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineShanghai, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical College, Beijing University of Chinese Medicine Beijing, China.
authors.forename: Linghui
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Bioinformatics, School of Life Sciences and Technology, Tongji University Shanghai, China.
authors.forename: Ruixin
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical College, Beijing University of Chinese Medicine Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
keywords: Acute myocardial infarction; Qishenyiqi; anti-inflammation; dyslipidaemia; group significance analysis