Targeting the NLRP3 by Natural Compounds: Therapeutic Strategies to Mitigate Doxorubicin-Induced Cardiotoxicity.

Abstract

Doxorubicin (DOX), a widely utilized anthracycline chemotherapy agent, is known for its potent anticancer efficacy across various malignancies. However, its clinical use is considerably restricted due to the risk of dose-dependent cardiotoxicity, which can lead to long-term heart dysfunction. The underlying mechanism of DOX-induced cardiotoxicity has been associated with the formation of reactive oxygen species (ROS) and disrupting cellular signaling pathways. This is particularly relevant to the activation of the NLRP3 inflammasome, which triggers inflammation and pyroptosis in cardiac cells. In recent years, there has been growing interest in natural compounds that exhibit potential cardioprotective effects against the adverse cardiac effects of DOX. The present study showed that specific natural compounds, such as honokiol, resveratrol, cynaroside, and curcumin, can confer significant protection against DOX-induced cardiotoxicity through the modulation of NLRP3 inflammasome signaling pathways. In summary, incorporating natural compounds into treatment plans could be a practical approach to improve the safety profile of DOX, thereby protecting cardiac health through the regulation of the NLRP3 pathway.