Targeting the NLRP3 Inflammasome in Atherosclerosis: Advances in Anti-Inflammatory Therapies With Bioactive Natural Products.

Atherosclerosis (AS) serves as the shared pathological substrate for cardiovascular and cerebrovascular diseases. The traditional passive-accumulation model centered on cholesterol no longer explains why lipid targets are met while clinical events persist and has therefore prompted a shift toward a combined anti-inflammatory and lipid-lowering strategy. Inflammasomes-particularly the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-integrate and amplify multiple pro-atherogenic signals and have emerged as a key target. However, no agent targeting NLRP3 has yet gained Food and Drug Administration (FDA) approval, and the unmet clinical need remains pressing. Natural products are considered a promising option for this chronic and multifactorial disease due to their favorable safety profile and multi-target effects. However, a narrative review of intervention strategies at various levels-from traditional Chinese medicine (TCM) formulas and plant extracts to natural compounds-is still lacking. We searched for publications from the past 4 years using PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus. This narrative review highlights the key role of NLRP3 inflammasome-related signaling pathways in the development of AS and evaluates the evidence for natural products targeting these pathways. Given the limitations of the available evidence, large-scale, high-quality randomized controlled trials are needed to establish clinical efficacy and safety.