Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation

Abstract Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti‐inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC‐derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)‐induced lipid accumulation and the upregulation of adipose differentiation‐associated protein Plin2 in a dose‐ and time‐responsive manner. We elucidated that Scu effectively diminishes OA‐provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B‐II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA‐induced decrement of LC3B‐II levels in the presence of bafilomycin‐a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross‐sectional area, wall‐to‐lumen ratio and serum total cholesterol levels in comparison to the high‐fat diet model group. Collectively, our findings suggest that Scu attenuates OA‐induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.