AbstractThe phytochemical investigation, including fractionation and purification of 70% acetone extracts of Juglans sigillata seed husks, an agricultural residue, led to the isolation of five low-molecular weight galloyltannins. The structures of the extractives were elucidated as 1,2,6-tri-O-galloyl-β-D-glucose (1), 3,4,6-tri-O-galloyl-β-D-glucose (2), 2,3,4,6-tetra-O-galloyl-β-D-glucose (3), 1,2,3,4,6-penta-O-galloyl-β-D-glucose (4), and tannic acid (5), primarily based on their spectral (NMR and MS) and chemical evidence. Galloyltannins 1-5 showed strong inhibitory activity against mushroom tyrosinase, with IC50 values ranging from 35.27 to 76.37 μM; kojic acid, which was used as a positive control, had an IC50 value of 342.14 μM. It was further found that 1-5 inhibited melanin production and exhibited intracellular tyrosinase activity, as well as down-regulated mRNA and protein expression levels of tyrosinase, in B16F10 mouse melanoma cells. Therefore, the isolated extractives from seed husks of J. sigillata may serve as potential candidates for hyperpigmentation remediation and as skin-whitening agents in the cosmetics industry.