Phlorizin in Apple Trees: From Horticultural Factors to Nutraceutical Applications

Phlorizin is a naturally occurring dihydrochalcone predominantly found in apple trees (Malus domestica), where it is one of the species' characteristic phenolic compounds. Its accumulation varies according to genotype, tissue type, developmental stage, environmental conditions, and cultivation practices. While these factors are fundamental for understanding phlorizin biosynthesis and distribution, growing attention has focused on its biological activities and potential health applications. This review provides an integrated overview of phlorizin, from its occurrence in apple plants to its emerging nutraceutical and biomedical relevance. Particular emphasis is placed on the molecular mechanisms underlying its antioxidant, anti-inflammatory, antimicrobial, antiviral, and metabolic effects. Phlorizin is best known for inhibiting sodium-glucose co-transporters (SGLT1 and SGLT2), a mechanism that inspired the development of synthetic SGLT inhibitors for metabolic diseases. Beyond glucose regulation, increasing evidence highlights its broader effects on lipid metabolism, gut microbiota modulation, neuroprotection, cardioprotection, hepatoprotection, anti-aging pathways, and tissue regeneration. Advances in extraction, purification, encapsulation, and delivery technologies are expanding its applications in functional foods, dietary supplements, and biomaterials. However, limited bioavailability and scarce clinical evidence remain key challenges. Overall, phlorizin represents a promising apple-derived phytochemical with significant potential for future health-oriented applications.