Centella asiatica Extract and Arbutin Hybrid Nanoemulsion as a Synergistic Inhibitor of Melanogenesis

Melanogenesis is the molecular process that produces melanin pigment in melanocytes. One of the well-known commercial anti-melanogenic agents is β-arbutin, which lacks stability and skin penetration. Previous studies combined β-arbutin and asiaticoside, a triterpenoid glycoside from Centella asiatica, to enhance antioxidant and antimelanogenic properties. This study aimed to formulate a hybrid nanoemulsion of β-arbutin and C. asiatica extract for synergistic inhibition of melanogenesis, supported by bioinformatics and molecular docking validation. Bioinformatics analysis was conducted to identify the gene targets of β-arbutin and asiaticoside in melanogenesis. The interaction of the compounds with tyrosinase (TYR) was examined through molecular docking. Before formulation, the extracts were identified for asiaticoside using thin-layer chromatography (TLC). Then, hybrid nanoemulsions of β-arbutin and asiaticoside combination were formulated and characterized for physicochemical stability and tested for tyrosinase inhibition and melanin suppression in B16F10 melanoma cells. TYR, Microphthalmia-associated Transcription Factor (MITF), and Dopachrome Tautomerase (DCT) were identified as major target genes that had strong binding affinities with TYR for asiaticoside (−6.38 kcal/mol) and β-arbutin (−6.23 kcal/mol). The optimized hybrid nanoemulsion (Fae) exhibited nanosized droplets (10.44 ± 0.28 nm), low polydispersity index PDI (<0.2), and high tyrosinase inhibition (91.54 ± 0.77%). Fae significantly reduced intracellular melanin production (13.08 ± 2.02%) compared to single formulations. This indicates that the β-arbutin and Centella asiatica hybrid nanoemulsion enhances TYR enzyme inhibition and cellular anti-melanogenic activity, presenting a promising natural-based approach for topical skin lightening and hyperpigmentation therapy.