The effects of apigenin on immune responses and inflammatory biomarkers in sepsis: a comprehensive systematic review

BACKGROUND: Apigenin, a flavonoid predominantly found in citrus fruits, particularly grapefruit, has attracted significant attention in ethnopharmacology for its diverse therapeutic properties. METHOD: This systematic review focuses on the potential therapeutic impact of Apigenin on sepsis complications. Google Scholar, Scopus, Web of Science, PubMed and Embase databases were searched for relevant keywords up to August 2025. RESULTS: A total of 421 articles were screened in the databases. Finally, only 30 studies remain. Evidence from in vivo and in vitro studies indicates that Apigenin modulates key signalling pathways, such as Rho-associated coiled-coil containing protein kinase (ROCK)/Ras homolog family member A (RhoA)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Peroxisome Proliferator-activated receptor gamma (PPARγ)/microRNA-21 (miR-21) and Kelch-like eCH-associated protein 1 (KEAP1)/Nuclear factor erythroid 2-related factor 2 (Nrf2), to alleviate sepsis-induced damage in organs such as the lungs, intestines, heart and kidneys. Additionally, Apigenin promotes macrophage polarization towards the M2 macrophage phenotype (M2) phenotype and reduces proinflammatory cytokines (Interleukin-6 (IL-6), Tumour necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β). CONCLUSION: Despite its promising effects, further clinical trials are needed to confirm its efficacy and safety in septic patients.

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