A NARRATIVE REVIEW OF PROPOLIS AND METFORMIN IN TOPICAL DERMATOLOGY: FROM MONO-AGENT BIOACTIVITIES TO THE FRONTIER OF EMULGEL-BASED COMBINATION THERAPIES FOR MELASMA

Melasma is a common, therapeutically challenging disorder of hyperpigmentation characterized by a complex pathophysiology involving aberrant melanogenesis, oxidative stress, and inflammation. Current gold-standard treatments are often limited by safety concerns or suboptimal efficacy. This narrative review synthesizes the literature from 2010 to 2026 to evaluate two promising agents for melasma therapy: propolis, a natural resin with multifaceted bioactivities, and metformin, a repurposed drug with a novel melanogenesis-inhibiting mechanism. We systematically examine the pharmacological properties of both agents, including their anti-melanogenic, antioxidant, anti-inflammatory, and photoprotective effects in skin models. The review further explores the evolution of their topical formulations, from conventional creams to advanced nano-delivery systems, highlighting the potential of emulgel technology as a superior platform. Finally, we assess the growing body of evidence supporting multi-target combination therapies for melasma. By consolidating this evidence, we establish the scientific rationale for a novel, unexplored therapeutic strategy: a dual-drug emulgel co-delivering metformin and propolis to synergistically target both upstream signaling and downstream enzymatic pathways in melanogenesis.