title: Astragaloside IV inhibits isoprenaline‑induced cardiac fibrosis by targeting the reactive oxygen species/mitogen‑activated protein kinase signaling axis.
abstract: Cardiac fibrosis is considered an important pathological mechanism in the progression of cardiac remodeling and heart failure. Astragaloside IV (AsIV) is a major active ingredient in Astragalus membranaceus. In a preliminary experiment, it was demonstrated that this naturally occurring substance exhibited cardioprotective effects via preventing cardiomyocyte hypertrophy and apoptosis. The present study aimed to investigate the effects of AsIV on β‑adrenergic receptor (β‑AR)‑mediated cardiac fibrosis, and the associated mechanism. Cell Counting Kit‑8 (CCK‑8) assay was used to examine the proliferation of rat cardiac fibroblast (CF) cultures. Collagen I secretion was detected by ELISA. Dihydroethidium was used to determine intracellular ROS levels. Western blotting was used to examine the expression level of total and phosphorylated mitogen‑activated protein kinases (MAPKs). In the present study, the effects of AsIV on β‑adrenergic receptor (β‑AR) ‑mediated cardiac fibrosis were investigated, and the associated mechanism was revealed. Isoprenaline (ISO) is a selective β‑AR agonist, and treatment with AsIV significantly inhibited (ISO)‑triggered cardiac fibroblast proliferation and type I collagen synthesis. In addition, ISO resulted in a significant elevation of reactive oxygen species (ROS) levels and phosphorylation of the three profibrotic MAPKs, namely extracellular signal‑regulated kinase, p38MAPK and c‑Jun N‑terminal kinase. AsIV effectively reversed the aforementioned ISO‑induced alterations. In addition, N‑acetylcysteine, a typical ROS scavenger, mimicked the inhibitory effects of AsIV on MAPK activation. The present study demonstrated that AsIV may inhibit ISO‑induced cardiac fibrosis by suppressing ROS‑mediated MAPK activation.
authors.affiliation: Department of Community Health Nursing, School of Nursing, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Meili
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Community Health Nursing, School of Nursing, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Community Health Nursing, School of Nursing, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D024042:Collagen Type I; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D048031:JNK Mitogen-Activated Protein Kinases; D007545:Isoproterenol