Mangiferin from coffee leaves: Integrative insights into extraction, bioactivity, molecular mechanisms, pharmacokinetics, advanced delivery systems, food and nutraceutical potential

Mangiferin (MGF), a C-glycosylase xanthone predominantly found in coffee leaves and other plant sources, exhibits potent antioxidant, anti-inflammatory, antidiabetic, anticancer, and neuroprotective activities. This review critically synthesizes current knowledge on MGF’s extraction from coffee leaves, biological activities, molecular mechanisms, pharmacokinetics, and applications in food and nutraceutical systems. MGF activates Nrf2/ARE (2–4-fold upregulation of antioxidant enzymes) while inhibiting NF-κB (60–75% reduction in p65 translocation) and NLRP3 inflammasome signaling, thereby lowering proinflammatory cytokines. It enhances AMPK activity (2–3-fold) and improves insulin sensitivity. Despite its significant biological potential, the oral bioavailability of native MGF is less than 5% due to poor aqueous solubility, low permeability, efflux transport, and extensive phase II conjugation; circulating species are predominantly glucuronides. Recent advances in extraction (microwave- and ultrasound-assisted, and supercritical fluid) and delivery systems like nanoencapsulation, liposomes, cyclodextrin complexes, and phospholipid phytosomes, which significantly enhance stability, solubility, and bioefficacy. Additionally, the integration of MGF into functional foods, beverages, active packaging, and nutraceuticals demonstrates promising potential for developing value-added products with health benefits. Utilizing coffee leaves as a sustainable source not only enhances the compound’s accessibility but also adds value to agricultural by-products. In conclusion, MGF represents a multifunctional compound with considerable therapeutic and industrial relevance. Future research should prioritize clinical validation, optimization of delivery systems, and scalable extraction technologies to fully harness its benefits in food, pharmaceutical, and nutraceutical applications.