Phytochemical Investigation and Tyrosinase Inhibitory Activity of Compounds from the Aerial Parts of Mussaenda pubescens Dryand.

Mussaenda pubescens Dryand. is a medicinal plant widely used in traditional medicine in Southeast Asia for the treatment of inflammation, skin-related disorders, and other health conditions. Despite its ethnopharmacological significance, scientific evidence regarding its bioactive constituents remains limited. In particular, no comprehensive study has been reported on the chemical constituents of M. pubescens in relation to tyrosinase-associated activity. In the present study, one new compound (1) and six known compounds (2-7) were isolated from the ethanol extract of the aerial parts of M. pubescens using various chromatographic techniques. Their structures were elucidated on the basis of extensive spectroscopic analyses, including NMR and HR-ESI-MS data. All isolated compounds were evaluated for their tyrosinase inhibitory activity. The results showed that compounds 1, 4, and 5 exhibited significant inhibitory effects, with IC50 values of 62.39 ± 0.48, 62.55 ± 0.49, and 178.06 ± 0.89 µM, respectively. The underlying inhibitory mechanisms against tyrosinase were further investigated through enzyme kinetic studies and molecular docking simulations. Enzyme kinetic analysis revealed that compound 1 acted as a competitive inhibitor of tyrosinase, with an inhibition constant (Ki) value of 22.28 ± 0.73 µM. Overall, M. pubescens was found to contain a diverse range of secondary metabolites, including iridoid glucosides, saponins, and flavonoids, which exhibited notable tyrosinase inhibitory activity. These findings provide the first chemical insight into the tyrosinase-related bioactivity of M. pubescens and support its potential application as a natural source of tyrosinase inhibitors for pharmaceutical and cosmetic purposes.