Inhibition of cardiotrophin-1 overexpression is involved in the anti-fibrotic effect of Astrogaloside IV

Abstract

Astragaloside IV (AsIV), one of the major active ingredients in Astragalus membranaceus, has demonstrated remarkable antifibrotic effects via its antioxidative activity. Cardiac fibrosis is an important pathological mechanism during cardiac remodelling associated with heart failure. In the present study, the mechanism underlying the antifibrotic effect of AsIV upon isoprenaline (ISO) stimulation was investigated. AsIV significantly improved cardiac fibrosis in vivo and dose‑dependently inhibited ISO‑induced CF proliferation in vitro. The ISO‑triggered elevation in reactive oxygen species (ROS) levels was remarkably inhibited by AsIV, as well as ROS scavenger N‑acetylcysteine (NAC), and not affected by cardiotrophin‑1 (CT‑1) knockdown. In addition, AsIV effectively reversed ISO‑induced upregulation of CT‑1 expression, which was blunted by pretreatment with NAC. Cardiac fibroblast (CF) proliferation and collagen Ι overexpression induced by ISO stimulation were effectively abrogated by AsIV, NAC, and CT‑1 small interfering RNA transfection. Taken together, these results demonstrated that AsIV was able to effectively inhibit ISO‑induced CF proliferation and collagen production through negative regulation of ROS‑mediated CT‑1 upregulation.

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

“…Also, relative heart weight was decreased by NAC supplementation. Similar results observed by Jia et al [66] who reported that cardiac broblast proliferation, collagen Ι and CT-1 overexpression induced by isoprenaline stimulation were effectively abrogated by NAC treatment.…”

<p>Astragaloside IV: An Effective Drug for the Treatment of Cardiovascular Diseases</p>

“…It has been found that both increased ROS content and upregulated cardiotrophin 1 (CT1) expression, both of which were inhibited after the addition of astragaloside, which inhibited cardiac fibroblast proliferation and collagen production. 71 Inhibition of ROS-mediated MAPK activation can also inhibit myocardial fibrosis. AS-IV can significantly inhibit ISO-induced cardiac fibroblast proliferation and collagen I synthesis, reduce ROS levels, and inhibit the phosphorylation of extracellular signal-regulated kinase, p38MAPK, and cJun N-terminal kinase.…”

A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics on Astragali Radix: Implications for Astragali Radix as a Personalized Medicine

“…An increasing number of experiments have confirmed that AR can effectively inhibit cardiovascular diseases such as myocardial ischemia-reperfusion injury [9], myocardial hypertrophy [58], vascular endothelial dysfunction [59], coronary heart disease [60], atherosclerosis [61], cardiac fibrosis [62] and viral myocarditis [63]. The main mechanisms of the treatment of cardiovascular diseases by AR and its main components are summarized in Figure 1.…”

“…Moreover, excessive ROS can promote the production of cardiotrophin-1 (CT-1), which can significantly promote cardiac fibrosis. AS-IV was also able to effectively inhibit isoproterenol-induced cardiac fibroblast proliferation and collagen production through negative regulation of ROS-mediated CT-1 upregulation [62] (Figure 1⑥).…”