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Thymoquinone (TQ), a bioactive component extracted from <jats:italic>Nigella sativa<\/jats:italic> 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\u2010challenged mice. The in vitro experiments showed that TQ treatment attenuated the PE\u2010induced hypertrophic response in NRCMs. Mechanistical experiments showed that supplementation of TQ induced reactivation of the AMP\u2010activated protein kinase (AMPK) with concomitant inhibition of ERK 1\/2, p38 and JNK1\/2\u00a0MAPK 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\u2010dependent manner and identified it as a promising agent for the treatment of myocardial hypertrophy.<\/jats:p>","DOI":"10.1111\/jcmm.17138","type":"journal-article","created":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T06:50:03Z","timestamp":1640415003000},"page":"855-867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Thymoquinone ameliorates pressure overload\u2010induced cardiac hypertrophy by activating the AMPK signalling pathway"],"prefix":"10.1111","volume":"26","author":[{"given":"Heng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiology and Atrial Fibrillation Center The First Affiliated Hospital College of Medicine Zhejiang University Hangzhou 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