Thymoquinone ameliorates pressure overload‐induced cardiac hypertrophy by activating the AMPK signalling pathway

Abstract

Prolonged pathological myocardial hypertrophy leads to end‐stage heart failure. Thymoquinone (TQ), a bioactive component extracted from Nigella sativa seeds, is extensively used in ethnomedicine to treat a broad spectrum of disorders. However, it remains unclear whether TQ protects the heart from pathological hypertrophy. This study was conducted to examine the potential utility of TQ for treatment of pathological cardiac hypertrophy and if so, to elucidate the underlying mechanisms. Male C57BL/6J mice underwent either transverse aortic constriction (TAC) or sham operation, followed by TQ treatment for six consecutive weeks. In vitro experiments consisted of neonatal rat cardiomyocytes (NRCMs) that were exposed to phenylephrine (PE) stimulation to induce cardiomyocyte hypertrophy. In this study, we observed that systemic administration of TQ preserved cardiac contractile function, and alleviated cardiac hypertrophy, fibrosis and oxidative stress in TAC‐challenged mice. The in vitro experiments showed that TQ treatment attenuated the PE‐induced hypertrophic response in NRCMs. Mechanistical experiments showed that supplementation of TQ induced reactivation of the AMP‐activated protein kinase (AMPK) with concomitant inhibition of ERK 1/2, p38 and JNK1/2 MAPK cascades. Furthermore, we demonstrated that compound C, an AMPK inhibitor, abolished the protective effects of TQ in in vivo and in vitro experiments. Altogether, our study disclosed that TQ provides protection against myocardial hypertrophy in an AMPK‐dependent manner and identified it as a promising agent for the treatment of myocardial hypertrophy.

Thymoquinone reverses homocysteine-induced endothelial dysfunction via inhibition of ER-stress induced oxidative stress pathway

“…The nding from our study agrees with these studies, whereby ROS level and NOX4 expression were elevated with homocysteine incubation and was normalised with TQ treatment. Moreover, TQ has been demonstrated as a possible drug for the treatment of cardiac hypertrophy since it protects against the disease by lowering NOX4 in an AMPK-dependent manner [59]. Previous studies showed that TQ act as an antioxidant, protects HUVECs against [40].…”

Natural Bioactive Compounds Targeting NADPH Oxidase Pathway in Cardiovascular Diseases

“…Furthermore, Chen et al reported that through the activation of AMPK and suppression of MAPK signalling in vivo and in vitro, TQ has a protective impact on pathological heart hypertrophy [ 127 ]. Transverse aortic constriction (TAC) or a sham procedure was performed on male C57BL/6J mice, and both procedures were followed by six weeks of TQ therapy.…”

The significance of thymoquinone administration on liver toxicity of diazinon and cholinesterase activity; a recommendation for prophylaxis among individuals at risk

“…In this context, earlier studies have demonstrated that presence of many quinones especially thymoquinone as natural antioxidants in N. sativa and its extract is responsible for the improvement of oxidative stress and the subsequent organ damages induced by some xenobiotic and chemicals. Recent researches on TQ in rats and mice have shown that this bioactive compound has cardioprotective, neuroprotective, and nephroprotective effects based on its anti-inflammatory properties [34][35][36][37][38][39][40]. Some animal studies have demonstrated that TQ has therapeutic benefits against brain injury, ovarian cyst formation, and tumor growth [34,39,41,42].…”