Abstract

Abstract The overactivation of β‐adrenergic receptors (β‐ARs) can result in acute myocardial ischemic injury, culminating in myocardial necrosis. Berberine (BBR) has exhibited promising potential for prevention and treatment in various heart diseases. However, its specific role in mitigating myocardial injury induced by acute β‐AR overactivation remains unexplored. This study aimed to investigate the effects and underlying mechanisms of BBR pretreatment in a rat model of acute β‐AR overactivation induced by a single dose of the nonselective β‐adrenergic agonist isoprenaline (ISO). Rats were pretreated with saline or BBR (100 mg/kg/day) via gavage for 14 consecutive days, followed by a subcutaneous injection of ISO or saline on the 14th day. The findings indicated that BBR pretreatment significantly attenuated myocardial injury in ISO‐stimulated rats, as evidenced by reduced pathological inflammatory infiltration, necrosis, and serum markers of myocardial damage. Additionally, BBR decreased oxidative stress and inflammation in the system and heart. Furthermore, BBR pretreatment enhanced myocardial ATP levels, improved mitochondrial dysfunction through increased Drp1 phosphorylation, and augmented myocardial autophagy. In a CoCl 2 ‐induced H9c2 cell hypoxic injury model, BBR pretreatment mitigated cellular injury, apoptosis, and oxidative stress while upregulating Drp1 and autophagy‐associated proteins. Mechanistically, BBR pretreatment activated AKT, AMPK, and LKB1 both in vivo and in vitro, implicating the involvement of the AKT and LKB1/AMPK signaling pathways in its cardioprotective effects. Our study demonstrated the protective effects of BBR against myocardial injury induced by acute β‐AR overactivation in rats, highlighting the potential of BBR as a preventive agent for myocardial injury associated with β‐adrenergic overactivation.