title: Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-α/PGC-1α signaling mediated energy biosynthesis.
abstract: We previously reported that Astragalus polysaccharide (APS) extracted from Chinese medicine Astragalus membranaceus (Fisch.) Bge, attenuates hypertrophy of neonatal rat ventricular myocytes (NRVMs) induced by isoproterenol (Iso). The present study was designed to investigate the effects and the possible mechanism of APS on Iso-induced hypertrophy in rats and NRVMs with focus on tumor necrosis factor α (TNF-α)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) signaling mediated energy biosynthesis. 36-Week old rats were randomly divided into 3 groups: (1) Control, rats received vehicle; (2) Iso, rats received isoproterenol injections; (3) Iso+APS, rats received isoproterenol injections and APS. NRVMs were divided into similar groups as rats. The results showed that combination of APS with Iso significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight (HW/BW) and left ventricular weight/BW (LVW/BW), improved the cardiac hemodynamics, down-regulated mRNA and protein expression of atrial natriuretic peptide (ANP), increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of free fatty acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with APS significantly decreased the surface area and protein content, down-regulated mRNA and protein expression of ANP, increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, APS increased the protein expressions of ATP5D, the σ subunit of ATP synthase, PGC-1α and pyruvate dehydrogenase kinase 4 (PDK4) in tissue and NRVMs respectively and inhibited the production of TNF-α in serum and culture medium compared with Iso alone. The results suggested that APS attenuates Iso-induced cardiac hypertrophy through regulating TNF-α/PGC-1α signaling mediated energy biosynthesis.
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001, PR China; Internal Medicine-Cardiovascular Department, The First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renming Jie, Jinzhou 121001, PR China.
authors.forename: Aina
authors.initials: A
authors.lastname: Luan
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001, PR China.
authors.forename: Futian
authors.initials: F
authors.lastname: Tang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001, PR China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001, PR China.
authors.forename: Meili
authors.initials: M
authors.lastname: Lu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, No. 40, Section 3, Songpo Road, Jinzhou 121001, PR China. Electronic address: hongxinwang@lnmu.edu.cn.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Internal Medicine-Cardiovascular Department, The First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renming Jie, Jinzhou 121001, PR China. Electronic address: zhangyingjiejinzhou@126.com.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D027885:Astragalus propinquus / Q000737:chemistry*; D006332:Cardiomegaly / Q000139:chemically induced / Q000517:prevention & control*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007267:Injections; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011134:Polysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011134:Polysaccharides; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007545:Isoproterenol
keywords: Astragalus polysaccharide; Cardiac hypertrophy; Energy biosynthesis; Hemodynamics; TNF-α/PGC-1α signaling