Mangiferin as a Multilevel Modulator of Metabolic Syndrome: Current Evidence and Future Perspectives

Background/Objectives: The obesogenic environment is a key factor in the rising prevalence of metabolic syndrome (MetS), a major global public health challenge. Mangiferin (Mgf) is a C-glycosylated xanthone, and its preventive and therapeutic potential stems from its multisystemic pharmacological profile. This review integrates findings on Mgf in the management of metabolic syndrome, aiming to identify gaps and propose prospective studies to enable the scaling up of Mgf for clinical applications. Methods: To this end, a literature search was conducted, the level of evidence was identified, and the available scientific information on Mgf in metabolic syndrome was synthesized from PubMed, Scopus, and Web of Science from 2016 to 2025. Results: Mgf improves overall metabolic dysfunction by activating the AMPK pathway, reduces inflammation by activating Nrf2, suppressing NF-κB, and decreasing pro-inflammatory mediators (COX-2, IL-6, NLRP3), modulates CB1 and PPAR receptors and other markers associated with obesity (adiponectin, leptin, resistin), as well as autophagy processes. However, most of the evidence comes from in silico, in vitro, and preclinical studies, with few clinical observations. Conclusions: This underscores the need to integrate studies on the correlation between the bioavailability of Mgf and norathyriol with the regulation of the microbiota, as well as their effects on metabolomic and epigenetic mechanisms in MetS.