Astragaloside IV inhibits isoprenaline‑induced cardiac fibrosis by targeting the reactive oxygen species/mitogen‑activated protein kinase signaling axis

Dai,Hongliang; Jia,Guizhi; Lu,Meili; Liang,Chunguang; Wang,Yue; Wang,Hongxin

doi:10.3892/mmr.2017.6220

Astragaloside IV inhibits isoprenaline‑induced cardiac fibrosis by targeting the reactive oxygen species/mitogen‑activated protein kinase signaling axis

Authors:
- Hongliang Dai
- Guizhi Jia
- Meili Lu
- Chunguang Liang
- Yue Wang
- Hongxin Wang
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Affiliations: Department of Community Health Nursing, School of Nursing, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: February 17, 2017 https://doi.org/10.3892/mmr.2017.6220
Pages: 1765-1770

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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.

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