Potensi Pleiotropik Kuersetin terhadap Modulasi Fenotipe Makrofag dan Stabilisasi Plak pada Aterosklerosis: Tinjauan Pustaka
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Introduction: Conventional therapy for atherosclerotic plaques focuses on controlling blood lipid levels. However, in patients with comorbid conditions such as diabetes mellitus and chronic kidney disease, plaque progression and rupture continue to proceed aggressively due to the intensification of programmed cell death cascades, namely pyroptosis and ferroptosis, even when LDL levels are normal. First-line statin therapy has a therapeutic gap because it is unable to halt these cell death cascades and carries long-term side effects. Quercetin, a natural flavonoid, emerges as a solution due to its pleiotropic effects. This literature review aims to examine the molecular efficacy of quercetin in restoring vascular endothelial function, modulating macrophage phenotypes, and inhibiting the ferroptosis and pyroptosis cascades to maintain vascular plaque stability. Method: This literature review identified and screened scientific articles published in the last five years from the electronic databases PubMed, ScienceDirect, and Google Scholar that met the inclusion criteria, resulting in seven relevant articles for analysis. Discussion: The results of the literature review indicate that at the endothelial level, quercetin reactivates the KEAP-1/Nrf2/GPX4 axis to suppress free radicals and block ferroptosis. In macrophages, quercetin inhibits the p38MAPK/p16 pathway to prevent cellular senescence and suppresses the NLRP3 inflammasome to inhibit pyroptosis. Furthermore, quercetin stimulates the Stat6/Arg-1 pathway to trigger the polarization of M1 macrophages into pro-resolving M2 macrophages, and suppresses the destructive enzyme MMP-9. These activities increase the thickness of the fibrous cap while improving blood lipid profiles. Conclusion: Quercetin shows strong potential as an adjunct therapy for atherosclerosis through the inhibition of ferroptosis, pyroptosis, and the stabilization of vascular plaques.
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Copyright (c) 2026 Muhammad Ardhan Hakim, Muhammad Rifqi Al Azim, Ghazir Rahman Najib
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