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Although proprotein convertase subtilisin\/kexin type 9 (PCSK9) is widely recognised for its involvement in low\u2010density lipoprotein receptor regulation and systemic lipid homeostasis, growing evidence indicates that PCSK9 also exerts a direct influence on macrophage inflammatory responses and intracellular lipid metabolism. Within atherosclerotic lesions, PCSK9 accelerates foam cell development by promoting oxidised low\u2010density lipoprotein uptake, impairing cholesterol efflux through ABCA1 downregulation and activating key inflammatory pathways, particularly those mediated by TLR4\/NF\u2010\u03baB and the NLRP3 inflammasome. This review emphasises recent findings that identify natural bioactive compounds as a novel and biologically relevant approach to counteracting PCSK9\u2010driven inflammatory foam cell formation. Compounds such as salvianolic acid B, curcumin, quercetin, fisetin and myricetin display broad antiatherogenic properties by concurrently regulating macrophage polarisation, limiting scavenger receptor expression, suppressing inflammasome activation and modulating PCSK9 expression or function. In contrast to monoclonal PCSK9 inhibitors, which primarily address lipid lowering, these natural agents offer integrated anti\u2010inflammatory and lipid\u2010modulatory effects at the cellular level. Collectively, the evidence discussed in this review positions PCSK9 modulation by natural compounds as an emerging therapeutic concept that links lipid dysregulation with vascular inflammation. This multitarget strategy may complement current lipid\u2010lowering therapies and support the development of more accessible and inflammation\u2010focused interventions for atherosclerosis.<\/jats:p>","DOI":"10.1155\/adpp\/3005975","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:28:26Z","timestamp":1787988506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PCSK9\u2010Mediated Inflammation in Foam Cell Formation and Exploring the Biologically Active Compounds Derived From Natural Resources"],"prefix":"10.1155","volume":"2026","author":[{"given":"Maharani Hestu Mukti","family":"Wisesa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisa 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