Natural Tyrosinase Inhibitors from Lycopodium japonicum

Natural tyrosinase inhibitors are an important group of compounds with cosmetical and medicinal applications. With the aim of finding new types of natural tyrosinase inhibitors from ornamental and medicinal plants, <i>Lycopodium japonicum</i> was selected and studied. As a result, fifteen structurally diverse secondary metabolites <b>1</b>-<b>15</b> were isolated and identified. Their chemical structures were identified by analysis of their spectral data and compared with those reported in the literature. In the tyrosinase inhibitory bioassay, five phytochemicals, <b>4</b>, <b>12</b>, <b>13</b>, <b>14,</b> and <b>15,</b> exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values ranging from 1.46 to 6.82 mM. Additionally, molecular docking studies disclosed that Lys376, Lys379, Gln307, and other amino acid residues played key roles in the potential binding interactions between the active compounds and the tyrosinase. These findings suggest that the species <i>L. japonicum</i> is a warehouse of natural tyrosinase inhibitors.