Sweroside alleviates pressure overload-induced heart failure through targeting CaMKⅡδ to inhibit ROS-mediated NF-κB/NLRP3 in cardiomyocytes
Heart failure is a major global health issue characterized by significant morbidity and mortality . Cardiac remodeling, which involves myocardial hypertrophy and fibrosis, is a key factor contributing to ventricular dysfunction in heart failure . Numerous recent clinical and experimental studies have emphasized the non-negligible role of abnormal inflammation in the pathogenesis of heart failure. Targeting inflammatory pathways will likely provide valuable therapeutic approaches to managing heart failure . Thus, investigating the role of inflammation in heart failure development is crucial for early identification of risk factors and implementing effective treatment strategies to enhance heart failure prognosis.
Studies conducted in clinical settings have revealed that individuals suffering from heart failure experience persistent low-grade inflammation within the heart. This inflammatory reaction has been linked to negative clinical outcomes . In heart failure induced by pressure overload, specifically through Ang II or TAC, cardiomyocytes are believed to be the source of the initial inflammatory response . CaMKIIδ within cardiomyocytes plays a role in NF-κB transcription and in regulating the assembly of the NLRP3 inflammasome. This process leads to an increased release of proinflammatory substances like IL-6, IL-1β, and IL-18. Elevated levels of these pro-inflammatory factors trigger the activation of cardiac fibroblasts, ultimately hastening the development of myocardial fibrosis in heart failure.
Natural products offer a valuable reservoir for drug development to address complex diseases, including heart failure . Pharmacokinetic studies of sweroside in rats showed that its absolute bioavailability was 11.90 % on average. Tissue distribution results showed that sweroside was mainly distributed in tissues with abundant blood-supply (kidneys, liver, spleen and lungs), and was also distributed in heart and brain tissues. We have previously demonstrated that sweroside, one of the main active components of Lonicerae Japonicae Flos, distributed in the heart tissue as original type and had biological properties that ameliorate cardiovascular disease . Prior research has shown that sweroside primarily exhibits antioxidant and anti-inflammatory properties, making it commonly utilized in China and other Asian nations for various purposes such as treating myocardial injury and hepatic steatosis . A recent study found that sweroside is anti-inflammatory to attenuate myocardial ischaemia-reperfusion injury, and the mechanism of its effect may be the inhibition of NLRP3 inflammasome . Sweroside has also demonstrated the ability to shield cardiomyocytes from aconitine-induced harm by preventing calcium overload and decreasing reactive oxygen species (ROS) levels . Despite these encouraging findings, the specific mechanisms underlying sweroside's actions remain unknown. Moreover, its effectiveness in addressing cardiac remodeling due to pressure overload remains to be explored.
