{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T04:12:58Z","timestamp":1782619978044,"version":"3.54.5"},"reference-count":121,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial \u201cresidual inflammatory risk\u201d persists, propelling the search for targeted immunopharmacological interventions. At the forefront of this inflammatory cascade is the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as a central orchestrator of vascular inflammation by linking metabolic dysregulation to the innate immune response. Atherogenic danger signals\u2014such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals\u2014trigger NLRP3 activation through reactive oxygen species (ROS) generation, lysosomal rupture, and potassium efflux. This, in turn, drives the maturation of pro-inflammatory cytokines (IL-1\u03b2 and IL-18) and initiates macrophage pyroptosis. In this review, we systematically evaluate the immunomodulatory potential of natural products\u2014both complex extracts and single bioactive compounds\u2014in inhibiting the NLRP3 inflammasome axis. We detail the pharmacological mechanisms by which these natural agents intercept inflammatory signaling at multiple stages: suppressing TLR4\/NF-\u03baB-mediated priming, scavenging mitochondrial ROS, and restoring autophagic flux via AMPK\/mTOR pathways to prevent inflammasome assembly. By critically analyzing these pathways, we highlight natural product-derived inhibitors as a promising class of immunomodulators capable of attenuating atherosclerotic progression and addressing the persistent challenge of residual inflammatory risk.<\/jats:p>","DOI":"10.3390\/ijms27083650","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the NLRP3 Inflammasome in Atherosclerosis: A Review of Natural Products and Their Molecular Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"given":"Su-Jin","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical & Engineering, College of BIT Convergence, Seowon University, Cheongju-si 28674, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Min","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical & Engineering, College of BIT Convergence, Seowon University, Cheongju-si 28674, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Eon","family":"You","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical & Engineering, College of BIT Convergence, Seowon University, Cheongju-si 28674, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical & Engineering, College of BIT Convergence, Seowon University, Cheongju-si 28674, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1016\/j.jacc.2020.11.021","article-title":"The Global Burden of Cardiovascular Diseases and Risks: A Compass for Global Action","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1332","DOI":"10.1016\/S2214-109X(19)30318-3","article-title":"World Health Organization cardiovascular disease risk charts: Revised models to estimate risk in 21 global regions","volume":"7","author":"Kaptoge","year":"2019","journal-title":"Lancet Glob. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.arcmed.2015.06.006","article-title":"Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease","volume":"46","author":"Barquera","year":"2015","journal-title":"Arch. Med. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5334\/gh.1288","article-title":"The Heart of the World","volume":"19","author":"Perel","year":"2024","journal-title":"Glob. Heart"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1161\/CIR.0b013e31820a55f5","article-title":"Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association","volume":"123","author":"Heidenreich","year":"2011","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1016\/j.jacc.2019.10.009","article-title":"The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond","volume":"74","author":"Mensah","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1146\/annurev.bi.46.070177.004341","article-title":"The low-density lipoprotein pathway and its relation to atherosclerosis","volume":"46","author":"Goldstein","year":"1977","journal-title":"Annu. Rev. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S376","DOI":"10.1194\/jlr.R800087-JLR200","article-title":"The LDL modification hypothesis of atherogenesis: An update","volume":"50","author":"Steinberg","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis--An inflammatory disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMra043430","article-title":"Inflammation, atherosclerosis, and coronary artery disease","volume":"352","author":"Hansson","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1161\/CIRCRESAHA.115.306301","article-title":"Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis","volume":"118","author":"Gimbrone","year":"2016","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cell.2011.04.005","article-title":"Macrophages in the pathogenesis of atherosclerosis","volume":"145","author":"Moore","year":"2011","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0092-8674(01)00238-0","article-title":"Atherosclerosis. the road ahead","volume":"104","author":"Glass","year":"2001","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1172\/JCI0216452","article-title":"Consequences of cellular cholesterol accumulation: Basic concepts and physiological implications","volume":"110","author":"Tabas","year":"2002","journal-title":"J. Clin. Invest."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/35025203","article-title":"Atherosclerosis","volume":"407","author":"Lusis","year":"2000","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1093\/eurheartj\/ehw024","article-title":"Residual inflammatory risk: Addressing the obverse side of the atherosclerosis prevention coin","volume":"37","author":"Ridker","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1161\/CIRCULATIONAHA.118.034032","article-title":"Inflammatory and Cholesterol Risk in the FOURIER Trial","volume":"138","author":"Bohula","year":"2018","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","article-title":"Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein","volume":"359","author":"Ridker","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1056\/NEJMoa2021372","article-title":"Colchicine in Patients with Chronic Coronary Disease","volume":"383","author":"Nidorf","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction","volume":"381","author":"Tardif","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.cell.2010.01.040","article-title":"The inflammasomes","volume":"140","author":"Schroder","year":"2010","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nri3452","article-title":"Activation and regulation of the inflammasomes","volume":"13","author":"Latz","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/nature08938","article-title":"NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"Duewell","year":"2010","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1002\/jcp.25930","article-title":"NLRP3 inflammasome: Its regulation and involvement in atherosclerosis","volume":"233","author":"Hoseini","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/CIRCRESAHA.118.311362","article-title":"NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis","volume":"122","author":"Grebe","year":"2018","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1089\/ars.2014.5994","article-title":"Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector?","volume":"22","author":"Abais","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"443","DOI":"10.5551\/jat.RV17001","article-title":"Role of NLRP3 Inflammasomes in Atherosclerosis","volume":"24","author":"Karasawa","year":"2017","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1056\/NEJMoa1809798","article-title":"Low-Dose Methotrexate for the Prevention of Atherosclerotic Events","volume":"380","author":"Ridker","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd4510","article-title":"The re-emergence of natural products for drug discovery in the genomics era","volume":"14","author":"Harvey","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/j.drudis.2014.08.006","article-title":"Multi-target approach for natural products in inflammation","volume":"19","author":"Koeberle","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107686","DOI":"10.1016\/j.pharmthera.2020.107686","article-title":"The strategies and techniques of drug discovery from natural products","volume":"216","author":"Zhang","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/art.41245","article-title":"Direct Binding to NLRP3 Pyrin Domain as a Novel Strategy to Prevent NLRP3-Driven Inflammation and Gouty Arthritis","volume":"72","author":"Yang","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kim, S.W., Lee, J.H., Kim, B., Yang, G., and Kim, J.U. (2023). Natural Products as the Potential to Improve Alzheimer\u2019s and Parkinson\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108827"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/nm.2538","article-title":"Atherosclerosis: Current pathogenesis and therapeutic options","volume":"17","author":"Weber","year":"2011","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1126\/science.1990440","article-title":"Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis","volume":"251","author":"Cybulsky","year":"1991","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev.immunol.021908.132620","article-title":"Immune and inflammatory mechanisms of atherosclerosis (*)","volume":"27","author":"Galkina","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrcardio.2009.228","article-title":"Monocytes in atherosclerosis: Subsets and functions","volume":"7","author":"Woollard","year":"2010","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/cvr\/cvv147","article-title":"Monocyte trafficking across the vessel wall","volume":"107","author":"Gerhardt","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1161\/01.ATV.15.5.551","article-title":"The response-to-retention hypothesis of early atherogenesis","volume":"15","author":"Williams","year":"1995","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/nature00804","article-title":"Subendothelial retention of atherogenic lipoproteins in early atherosclerosis","volume":"417","author":"Gustafsson","year":"2002","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1161\/01.ATV.0000229218.97976.43","article-title":"Scavenger receptors in atherosclerosis: Beyond lipid uptake","volume":"26","author":"Moore","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"49982","DOI":"10.1074\/jbc.M209649200","article-title":"Scavenger receptors class A-I\/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages","volume":"277","author":"Kunjathoor","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1038\/emm.2014.38","article-title":"CD36, a scavenger receptor implicated in atherosclerosis","volume":"46","author":"Park","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1161\/CIRCRESAHA.110.224766","article-title":"The role of endoplasmic reticulum stress in the progression of atherosclerosis","volume":"107","author":"Tabas","year":"2010","journal-title":"Circ. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular Smooth Muscle Cells in Atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1161\/ATVBAHA.107.159327","article-title":"Role of smooth muscle cells in the initiation and early progression of atherosclerosis","volume":"28","author":"Doran","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1161\/ATVBAHA.108.173898","article-title":"Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability","volume":"28","author":"Newby","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1172\/JCI67526","article-title":"Collagenases and cracks in the plaque","volume":"123","author":"Libby","year":"2013","journal-title":"J. Clin. Invest."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"C13","DOI":"10.1016\/j.jacc.2005.10.065","article-title":"Pathology of the vulnerable plaque","volume":"47","author":"Virmani","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrcardio.2014.62","article-title":"Clinical classification of plaque morphology in coronary disease","volume":"11","author":"Otsuka","year":"2014","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.cell.2014.04.007","article-title":"Mechanisms and functions of inflammasomes","volume":"157","author":"Lamkanfi","year":"2014","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and Regulation of NLRP3 Inflammasome Activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/JLB.3MR0720-513R","article-title":"NLRP3 inflammasome priming: A riddle wrapped in a mystery inside an enigma","volume":"108","author":"McKee","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/ni.1703","article-title":"The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis","volume":"10","author":"Franchi","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"36617","DOI":"10.1074\/jbc.M112.407130","article-title":"Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation","volume":"287","author":"Juliana","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/nri2725","article-title":"NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production?","volume":"10","author":"Tschopp","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.immuni.2013.05.016","article-title":"K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter","volume":"38","author":"Kuffa","year":"2013","journal-title":"Immunity"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.immuni.2018.04.032","article-title":"The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation","volume":"49","author":"Di","year":"2018","journal-title":"Immunity"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/ni.1631","article-title":"Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization","volume":"9","author":"Hornung","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.immuni.2012.01.009","article-title":"Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis","volume":"36","author":"Shimada","year":"2012","journal-title":"Immunity"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/nature16959","article-title":"NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux","volume":"530","author":"He","year":"2016","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2016.58","article-title":"Inflammasomes: Mechanism of assembly, regulation and signalling","volume":"16","author":"Broz","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1161\/CIRCULATIONAHA.113.002714","article-title":"Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility","volume":"128","author":"Xiao","year":"2013","journal-title":"Circulation"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Gallego, P., Luque-Sierra, A., Falcon, G., Carbonero, P., Grande, L., Bautista, J.D., Mart\u00edn, F., and Del Campo, J.A. (2021). White Button Mushroom Extracts Modulate Hepatic Fibrosis Progression, Inflammation, and Oxidative Stress In Vitro and in LDLR\u2212\/\u2212 Mice. Foods, 10.","DOI":"10.3390\/foods10081788"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15506","DOI":"10.1021\/acs.jafc.3c01966","article-title":"Apple Polyphenol Extract Ameliorates Atherosclerosis and Associated Cognitive Impairment through Alleviating Neuroinflammation by Weakening TLR4 Signaling and NLRP3 Inflammasome in High-Fat\/Cholesterol Diet-Fed LDLR(\u2212\/\u2212) Male Mice","volume":"71","author":"Yang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s12012-019-09534-9","article-title":"The Protective Effect of Crataegus aronia Against High-Fat Diet-Induced Vascular Inflammation in Rats Entails Inhibition of the NLRP-3 Inflammasome Pathway","volume":"20","author":"Shatoor","year":"2020","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.1002\/ptr.8321","article-title":"Ginkgo Flavone Aglycone Ameliorates Atherosclerosis via Inhibiting Endothelial Pyroptosis by Activating the Nrf2 Pathway","volume":"38","author":"Chen","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"155827","DOI":"10.1016\/j.phymed.2024.155827","article-title":"Guizhitongluo Tablet inhibits atherosclerosis and foam cell formation through regulating Piezo1\/NLRP3 mediated macrophage pyroptosis","volume":"132","author":"Pan","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/1061186X.2019.1616296","article-title":"Artemisinin alleviates atherosclerotic lesion by reducing macrophage inflammation via regulation of AMPK\/NF-\u03baB\/NLRP3 inflammasomes pathway","volume":"28","author":"Jiang","year":"2020","journal-title":"J. Drug Target."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1479164120977441","DOI":"10.1177\/1479164120977441","article-title":"Baicalin ameliorates atherosclerosis by inhibiting NLRP3 inflammasome in apolipoprotein E-deficient mice","volume":"17","author":"Zhao","year":"2020","journal-title":"Diab Vasc. Dis. Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Mao, J., Chen, Y., Zong, Q., Liu, C., Xie, J., Wang, Y., Fisher, D., Hien, N.T.T., Pronyuk, K., and Musabaev, E. (2024). Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 signaling pathway in vitro and in vivo. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1364161"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"121","DOI":"10.24976\/Discov.Med.202436180.11","article-title":"Mechanism of Curcumin Inhibiting NLRP3 Inflammatory Body and Improving Atherosclerotic Endothelial Cell Injury","volume":"36","author":"Ruan","year":"2024","journal-title":"Discov. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/s12944-024-02263-1","article-title":"Dihydromyricetin suppresses endothelial NLRP3 inflammasome activation and attenuates atherogenesis by promoting mitophagy","volume":"23","author":"Hu","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1007\/s10557-024-07659-w","article-title":"Emodin Suppresses NLRP3\/GSDMD-induced Inflammation via the TLR4\/MyD88\/NF-\u03baB Signaling Pathway in Atherosclerosis","volume":"39","author":"Ye","year":"2025","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"116304","DOI":"10.1016\/j.jep.2023.116304","article-title":"Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome","volume":"309","author":"Zhang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jare.2025.04.029","article-title":"Resibufogenin protects against atherosclerosis in ApoE(\u2212\/\u2212) mice through blocking NLRP3 inflammasome assembly","volume":"80","author":"Xiaoyang","year":"2026","journal-title":"J. Adv. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"155002","DOI":"10.1016\/j.phymed.2023.155002","article-title":"Salvianolic acid B inhibits atherosclerosis and TNF-\u03b1-induced inflammation by regulating NF-\u03baB\/NLRP3 signaling pathway","volume":"119","author":"Zhao","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e13845","DOI":"10.1111\/1440-1681.13845","article-title":"Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation","volume":"51","author":"Gao","year":"2024","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/eurheartj\/ehaa099","article-title":"Targeting cardiovascular inflammation: Next steps in clinical translation","volume":"42","author":"Lawler","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Hua, Z., Wang, X., Qin, L.L., Zhu, K.P., Li, D.Y., Zhang, X.Y., Zhang, L., and Zhai, F.T. (2025). Plant-derived natural products targeting inflammation in treatment of atherosclerosis. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1642183"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41569-020-0431-7","article-title":"Ageing and atherosclerosis: Vascular intrinsic and extrinsic factors and potential role of IL-6","volume":"18","author":"Tyrrell","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1749-6632.2010.05842.x","article-title":"Bioavailability of resveratrol","volume":"1215","author":"Walle","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/ajcn\/79.5.727","article-title":"Polyphenols: Food sources and bioavailability","volume":"79","author":"Manach","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1021\/acs.jmedchem.6b00975","article-title":"The Essential Medicinal Chemistry of Curcumin","volume":"60","author":"Nelson","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ctim.2011.09.004","article-title":"Quality of herbal medicines: Challenges and solutions","volume":"20","author":"Zhang","year":"2012","journal-title":"Complement. Ther. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.chroma.2014.10.091","article-title":"Current approaches and challenges for the metabolite profiling of complex natural extracts","volume":"1382","author":"Wolfender","year":"2015","journal-title":"J. Chromatogr. A"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/ATVBAHA.111.237693","article-title":"Animal models of atherosclerosis","volume":"32","author":"Getz","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1161\/CIRCRESAHA.116.308334","article-title":"Atherosclerosis: Successes, Surprises, and Future Challenges","volume":"118","author":"Libby","year":"2016","journal-title":"Circ. Res."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ding, N., Wei, B., Fu, X., Wang, C., and Wu, Y. (2020). Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.591393"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"104375","DOI":"10.1016\/j.drudis.2025.104375","article-title":"NLRP3 inflammasome: From drug target to drug discovery","volume":"30","author":"Yin","year":"2025","journal-title":"Drug Discov. Today"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"10210","DOI":"10.1002\/anie.201601967","article-title":"Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel Lecture)","volume":"55","author":"Tu","year":"2016","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"107100","DOI":"10.1016\/j.phrs.2024.107100","article-title":"Novel nano-drug delivery system for natural products and their application","volume":"201","author":"Huang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Cardoso, R.V., Pereira, P.R., Freitas, C.S., and Paschoalin, V.M.F. (2022). Trends in Drug Delivery Systems for Natural Bioactive Molecules to Treat Health Disorders: The Importance of Nano-Liposomes. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122808"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2147\/IJN.S443692","article-title":"Nano-Drug Delivery Systems Based on Natural Products","volume":"19","author":"Lv","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"rbad069","DOI":"10.1093\/rb\/rbad069","article-title":"Nature-inspired nanocarriers for improving drug therapy of atherosclerosis","volume":"10","author":"Ji","year":"2023","journal-title":"Regen. Biomater."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e04990","DOI":"10.1002\/advs.202504990","article-title":"Nanoparticle Drug Delivery Systems for Atherosclerosis: Precision Targeting, Inflammatory Modulation, and Plaque Stabilization","volume":"12","author":"Zhang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Luo, T., Zhang, Z., Xu, J., Liu, H., Cai, L., Huang, G., Wang, C., Chen, Y., Xia, L., and Ding, X. (2023). Atherosclerosis treatment with nanoagent: Potential targets, stimulus signals and drug delivery mechanisms. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1205751"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Hu, G., Guo, M., Xu, J., Wu, F., Fan, J., Huang, Q., Yang, G., Lv, Z., Wang, X., and Jin, Y. (2019). Nanoparticles Targeting Macrophages as Potential Clinical Therapeutic Agents Against Cancer and Inflammation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01998"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12951-025-03921-x","article-title":"Macrophage membrane-coated nanoparticles in inflammatory diseases: From bioinspired design to translational potential","volume":"24","author":"Hou","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/17460441.2016.1272757","article-title":"The structural modification of natural products for novel drug discovery","volume":"12","author":"Yao","year":"2017","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/CIRCRESAHA.115.306656","article-title":"From C-Reactive Protein to Interleukin-6 to Interleukin-1: Moving Upstream To Identify Novel Targets for Atheroprotection","volume":"118","author":"Ridker","year":"2016","journal-title":"Circ. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4330574","DOI":"10.1155\/mi\/4330574","article-title":"NLRP3 Inflammasome: A New Target for the Treatment of CVD and Depression Comorbidity","volume":"2025","author":"Chen","year":"2025","journal-title":"Mediators Inflamm."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.atherosclerosis.2020.08.019","article-title":"Residual inflammatory risk: Lessons from trials for the future","volume":"311","author":"Stock","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"c332","DOI":"10.1136\/bmj.c332","article-title":"CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials","volume":"340","author":"Schulz","year":"2010","journal-title":"BMJ"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3650\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T04:25:33Z","timestamp":1777091133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,19]]},"references-count":121,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083650"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083650","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,19]]}}}