LC-QTOF-MS/MS-Based Metabolomics Profiling and Tyrosinase Inhibitory Activity of Garcinia fruticosa Lauterb. Stem-Bark Extracts

Garcinia fruticosa Lauterb. (Clusiaceae) has been utilized as a skin-lightening agent. However, scientific data regarding its active metabolites remains remarkably limited. This study evaluates the metabolite profiles of methanol, ethyl acetate, and n-hexane extracts of G. fruticosa using LC-MS/MS coupled with chemometric analysis. The resulting metabolite profiles were correlated with tyrosinase inhibitory activity data using a partial least squares (PLS) approach. The chemometric analysis revealed distinct separation among the three extracts, indicating unique metabolite fingerprints for each solvent. Key discriminative metabolites identified across the extracts included kaempferol-related features (RT 5.72, 9.65, 10.33, 11.55, 11.95, and 12.38 min), Kuwanon K (RT 15.07 min), baicalein-6-glucuronide (RT 13.86 min), baicalein-7-O-β-D-glucopyranoside (RT 9.35 min) and four unidentified features (RT 4.05, 9.50, 15.49, and 17.20 min). Biological activity assays demonstrated that the 490 µg/mL ethyl acetate extract exhibited the highest inhibition at 37.82 ± 3.58%, followed by 500 µg/mL methanol (28.09 ± 0.60%) and 580 µg/mL n-hexane (25.33 ± 1.09%). PLS bi-plot analysis and variable importance in projection (VIP) scores indicated that the kaempferol-related features, especially 8-C-prenylkaempferol, kuwanon K, and 2’’-O-feruloylaloesin within the ethyl acetate extract were putatively annotated features associated with tyrosinase inhibitory. To the best of our knowledge, this is the first LC-MS/MS metabolomics study of G. fruticosa to identify potential tyrosinase inhibitory through chemometric correlation.