Mangiferin in human disease: Multifaceted mechanisms and applications (Review)

Mangiferin (MGF) is a natural C‑glucosyl xanthone with multitarget activity relevant to metabolic, inflammatory and cancer diseases. Notably, MGF modulates AMP‑activated protein kinase, NF‑κB, PI3K/AKT and MAPK signaling; through these pathways, it affects glucose and lipid metabolism, oxidative stress, apoptosis and inflammatory responses. In metabolic disorders, MGF has been shown to improve insulin sensitivity, support mitochondrial function and reduce diabetic complications. In cancer models, MGF suppresses proliferation, invasion and angiogenesis, and can influence antitumor immunity in the tumor microenvironment. Anti‑inflammatory actions include decreased cytokine release and regulation of the NLR family pyrin domain‑containing 3 inflammasome. Notably, clinical translation remains limited due to its low aqueous solubility, poor oral bioavailability and rapid metabolism. However, benefits of nanocarrier delivery, structural optimization and combination therapy have been reported, which may improve exposure and efficacy in experimental systems. Furthermore, safety signals in animals are favorable at relevant doses, but clinical evidence remains limited. In conclusion, the present review summarizes the pharmacodynamics and mechanisms of MGF across major disease settings and identifies key gaps for translation. Priorities include standardized clinical trials, optimization of delivery strategies, and rigorous assessment of long‑term safety and efficacy.