Oxyresveratrol extracted from Artocarpus heterophyllus Lam. inhibits tyrosinase and age pigments in vitro and in vivo.

We extracted and purified oxyresveratrol (OXY) from Artocarpus heterophyllus Lam. and identified its structure. The kinetics and mechanisms of OXY-induced mushroom tyrosinase inhibition were studied using fluorescence spectroscopy, copper ion chelation, and circular dichroism (CD). We found that OXY significantly inhibited tyrosinase with a half maximal inhibitory concentration (IC50) of 0.03 mM. The inhibitory effect of OXY on tyrosinase was almost 25 times that of kojic acid, which had an IC50 of 0.78 mM. Additionally, OXY and the tyrosinase substrate L-dopa did not have a competitive relationship; OXY is a non-competitive inhibitor. Using a fluorescence quenching experiment, we determined the corresponding rate constant (Kq) values at 298, 303, and 310 K to be 2.24 × 1012, 1.08 × 1012 and 1.44 × 1012 L mol-1 s-1, respectively. The OXY and tyrosinase interaction occured mainly through van der Waals forces and a hydrogen bond between the -OH group and its amino acid residue. Furthermore, we investigated the effects of OXY on murine melanoma B16 cells and on age pigments in Caenorhabditis elegans (C. elegans). OXY decreased melanin production by inhibiting the tyrosinase activity in murine melanoma B16 cells, which decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH) and increased catalase (CAT), leading to apoptosis. The lifespan of nematodes in the 50 ml resveratrol-treated group was significantly longer than that in the blank group by 5%. The mean lifespan of nematodes in the 50 μM OXY-treated group was significantly longer than that in the blank group by 6.82%.The fluorescence intensity of C. elegans pigments decreased by 30.43%, 47.35% and 64.42% after the treatment with a low, middle, and high OXY dose, respectively, showing that OXY has a significant inhibitory effect on melanin and age pigment production.