The cardioprotective effects of icariin on the isoprenaline-induced takotsubo-like rat model: Involvement of reactive oxygen species and the TLR4/NF-κB signaling pathway

Abstract

Introduction: Takotsubo syndrome (TS) is an acute cardiac syndrome that mimics acute coronary syndrome (ACS) but lacks coronary obstruction and is associated with sudden physical or psychiatric episodes. Several hypotheses have been proposed for the TS mechanism, but the precise cause of this syndrome remains poorly known. Recent studies noted TS patients with acute endogenous catecholamine discharge, which could trigger an oxidative stress response and inflammatory action.

Methods: A single dose of the selective β-adrenergic agonist isoprenaline (ISO) was used to induce a takotsubo-like (TS-like) model. Different icariin or metoprolol doses were supplied as cardioprotective agents by intragastric administration (IG), and lipopolysaccharides (LPS) were assessed to investigate the possible mechanism of action of icariin. Transthoracic echocardiography was used to study cardiac function and morphology. The amounts of intracellular lipids and myocardial fibrosis, which represent the degree of cardiac impairment, were assessed by histological analysis. Real-time polymerase chain reaction (RT-PCR) was performed to analyze a variety of anti-oxidant elements and inflammatory factors, and Western blotting was conducted to analyze the expression of signaling pathway proteins involved in the development of TS.

Results: The TS-like incidence in rats was lowest with icariin precondition at 2-h post-ISO administration, and both the left ventricular ejection fraction (LVEF) and ejection volume per minute were higher than those of the other groups. However, LPS administration increased the incidence of TS and aggravated cardiac impairment. Moreover, ISO significantly increased the levels of both reactive oxygen species (ROS) and TLR4/NF-κB signaling pathway proteins compared to those of the Sha-group, whereas icariin remarkably decreased the ROS levels and increased anti-oxidant element expression while reducing pro-inflammatory factor secretion and suppressing TLR4/NF-κB signaling pathway protein expression. However, the cardioprotective effect of icariin was significantly weakened by combining treatment with LPS.

Conclusion: Icariin prevented ISO-induced TS-like cardiac dysfunction in rats. The effects were induced mainly through maintenance of the dynamic balance of the ROS system, promotion of anti-oxidant element activity, and suppression of TLR4/NF-κB signaling pathway protein expression. Furthermore, the ability of icariin to increase anti-inflammatory and reduce pro-inflammatory factor secretion may be involved in the protective process.

Keywords: Icariin; Reactive oxygen species; TLR4/NF-κB signaling pathway; Takotsubo.