A Narrative Review of the Multi-Target Mechanisms of Glabridin in Skin Lightening.

BACKGROUND: Hyperpigmentation disorders are a leading cause of dermatological consultation worldwide. Conventional depigmenting agents such as hydroquinone and kojic acid primarily target tyrosinase, but their efficacy is limited by safety concerns and single-mechanism action. There is growing interest in natural multi-target compounds that modulate melanogenesis through complementary pathways. OBJECTIVE: This review summarizes the diverse molecular mechanisms through which glabridin, a prenylated isoflavan from Glycyrrhiza glabra root, exerts skin-lightening effects. METHODS: A comprehensive literature search was conducted in PubMed and Web of Science. Studies reporting the effects of glabridin on melanogenesis, inflammation, melanosome transfer, and melanosome degradation were evaluated. RESULTS: Glabridin inhibits tyrosinase activity and regulates melanogenic gene transcription. It also suppresses NF-κB-mediated inflammation, inhibits melanosome transfer through suppression of dendritic elongation, and promotes autophagy-mediated melanosome degradation. Additionally, this review addresses pharmacokinetic limitations, particularly poor aqueous solubility and bioavailability, and discusses formulation strategies designed to overcome them. CONCLUSION: Glabridin is a multi-target depigmenting agent that exerts skin-lightening effects through modulation of multiple nodes within the melanogenesis cascade, while maintaining an improved safety profile. This review provides an integrated perspective on the diverse biological activities of glabridin, bridging mechanistic insights with formulation advances to highlight its therapeutic potential in depigmentation. Further clinical trials are warranted to establish its therapeutic role in hyperpigmentation disorders.