Tyrosinase inhibition by natural stilbenoid glycosides: Critical role of the vinyl moiety in piceid for melanogenesis suppression

Abstract

<p>Skin hyperpigmentation due to UV-induced tyrosinase activation and melanin overproduction is an ongoing challenge in cosmetic and dermatological applications. While resveratrol analogues show anti-melanogenic potential, the structure-activity relationships of their glycosylated derivatives remain underexplored. Here, we investigate how the vinyl moiety in the food-derived stilbenoid glycoside piceid (resveratrol-3-O-β-glucoside) affects tyrosinase inhibition. We reduced the vinyl moiety to yield dihydropiceid by catalytic hydrogenation and systematically assessed both compounds for anti-melanogenic effects. As results, piceid exhibited superior monophenolase inhibition over dihydropiceid in enzyme kinetics, while both compounds showed comparable diphenolase inhibition. Cellular assays revealed that piceid reduced melanin production by 59.2 % at 25 μM in α-MSH-stimulated B16F10 melanoma cells, whereas dihydropiceid showed weaker activity (<25 % reduction). MolgpKa analysis indicated that the vinyl moiety lowered the 4′-OH pKa (9.7 vs. 9.9), while UV–vis spectroscopy validated that the vinyl moiety enhanced the copper chelation capacity of piceid (ΔOD: 0.459) over dihydropiceid (ΔOD: 0.233). Molecular docking revealed that 4′-OH in piceid closely coordinated the tyrosinase binuclear copper center, whereas molecular dynamics simulation validated that hydrogen bonding supports the binding of both compounds to tyrosinase. Collectively, this study establishes the vinyl moiety in dietary stilbenoids as a critical pharmacophore for tyrosinase inhibition and thereby provides a molecular basis for developing natural anti-hyperpigmentation functional foods or cosmeceuticals.</p>