Charting the Therapeutic Landscape of Naringin in Osteopathic and Metabolic Medicine

Disruption of skeletal homeostasis poses substantial risks to aging populations. Naringin, a flavonoid from Citrus paradisi and Drynariae Rhizoma, shows promise as a multitarget therapeutic agent for bone disorders.

This review systematically examines published literature on naringin's mechanisms in bone metabolism, analyzing signaling pathways, cellular interactions, and delivery systems through comprehensive database searches.

As a prodrug, naringin must be hydrolyzed to its active aglycone, naringenin. Naringenin promotes osteogenesis via Wnt/β-catenin, BMP-2/Smad, and the naringenin-activated estrogen receptor pathway while inhibiting osteoclastogenesis through RANKL/RANK/OPG modulation. Naringin demonstrates dual functionality by protecting normal bone tissue while inducing ferroptosis in osteosarcoma cells.

Naringin's pleiotropic effects address multiple pathological processes in skeletal disorders, including inflammation, oxidative stress, and metabolic dysregulation. Its interaction with gut microbiota and systemic metabolic pathways provides additional therapeutic benefits.

Naringin represents a promising natural therapeutic candidate for skeletal diseases. Key clinical translation gaps include the absence of fracture‑endpoint trials, insufficient bioavailability solutions, and unknown long‑term safety in humans. Future research should focus on advanced delivery systems and well‑designed randomized controlled trials.