Myocardial remodeling, which is a widely recognized independent risk factor for cardiac events (Xie et al., 2022; Yin et al., 2022; Zhou et al., 2022), is typically characterized by cardiac hypertrophy (Li et al., 2022b), myocardial fibrosis, and inflammation (Halade and Lee, 2022). Myocardial remodeling leads to heart failure (Oka et al., 2014), which has become a significant public health concern due to its high rates of occurrence and mortality (Lan et al., 2022). Existing therapeutic drugs primarily regulate blood pressure, enhance heart function, and reduce cardiac load. Commonly used drugs include angiotensin-converting enzyme inhibitors such as enalapril and captopril, calcium channel blockers such as amlodipine and nifedipine and β receptor blockers such as metoprolol and atenolol. However, prolonged use of these drugs can result in significant side effects, including dry cough (Liang et al., 2021), and angioedema (Quickfall et al., 2021). Due to the side effects associated with existing drugs, there is an urgent need to develop drugs that inhibit cardiac remodeling and prioritize safety.

The incidence of hypertension is high; an estimated 1.39 billion adults worldwide had hypertension in 2010, and it is a major cause of ventricular remodeling (Mills et al., 2020). The DOCA salt-sensitive hypertension model is commonly used in animal experiments to simulate hypertension-induced ventricular remodeling in humans (Hao et al., 2023; Zhou et al., 2020). Several studies have consistently shown that the endothelin system becomes activated in the DOCA-salt hypertension model (Chen et al., 2012; Larouche and Schiffrin, 1999). This activation leads to the binding of endothelin to its receptor in the heart, which in turn promotes ventricular remodeling (Dhaun and Webb, 2019). The PI3K/AKT/NFκB pathway is known to be crucial in endothelin-mediated myocardial remodeling (Fang et al., 2023; Li et al., 2022a). Endothelin activates the PI3K/AKT/NFκB pathway, which promotes the proliferation and growth of cardiomyocytes (Archer et al., 2017). However, excessive activation of this pathway can result in abnormal cardiomyocyte proliferation and ultimately trigger cardiac remodeling (Proud, 2004; Sun et al., 2021). Consequently, inhibiting the abnormal increase in endothelin and the PI3K/AKT/NFκB pathway may be a potential therapeutic approach for treating myocardial remodeling.

Salidroside (Fig. 1A), which is an active component extracted from the plant Rhodiola rosea, has shown therapeutic effects on cardiovascular diseases by exerting antioxidant (Sun et al., 2020) and anti-inflammatory effects (Fouda et al., 2022). Experimental studies have indicated that salidroside may play a role in reducing blood pressure and enhancing circulation, potentially by influencing vascular endothelial function (Wang et al., 2020b). These findings suggest that cardioprotective effect of salidroside could be associated with endothelin (Xing et al., 2020). Salidroside has shown effective cardiovascular protection in the context of doxorubicin-induced (Chen et al., 2022; Yan et al., 2021) cardiac dysfunction and diabetic cardiovascular disease (Ni et al., 2021; Wei et al., 2020). However, research on the DOCA-salt hypertension-induced myocardial remodeling model has not been reported. This study aimed to investigate the effect and mechanism of salidroside in the DOCA-salt-induced myocardial remodeling model.