Novel and Potential Photoprotective and Tyrosinase Inhibitory Effects of Tetrastigma erubescens Extracts: Evidence from In Vitro Assays and Computational Approach

<i>Tetrastigma erubescens</i>, a native medicinal plant of Vietnam, has long been used in folk medicine to manage various diseases, including skin-related issues. However, limited research has been conducted on this herb's bioactivities and chemical composition. This study aims to investigate the chemical constituents and evaluate the anti-tyrosinase activity and UV-A/UV-B absorption capacity of <i>T. erubescens</i> extracts, highlighting their potential as natural sources for skin-whitening and sun protection agents. In vitro assays demonstrated that the ethyl acetate (EA) extract of <i>T. erubescens</i> exhibited a significant UV-A and UV-B absorption capacity. Notably, this extract showed a strong anti-tyrosinase activity for the first time, with a maximum inhibition rate of 99.2% and an IC₅₀ value of 70.3 µg/mL. Based on the UHPLC and GCMS analysis, phenolic compounds (<b>1</b>-<b>9</b>) and ten volatile constituents (<b>10</b>-<b>19</b>) were identified in the EA extract of <i>T. erubescens</i>. Of these, almost all volatiles and some phenolics were reported for the first time in this genus. The molecular docking analysis revealed that all identified phytochemicals showed a comparable or greater binding affinity to both mushroom tyrosinase (docking scores: from -7.5 to -14.1 kcal/mol) and human tyrosinase (from -6.7 to -14.8 kcal/mol) than kojic acid (-8.7 and -8.6 kcal/mol, respectively). In addition, these identified compounds showed favorable drug-like properties and low toxicity risks via ADMET prediction and Lipinski's Rule of Five analyses. The results obtained in this work suggest that the EA extract of <i>T. erubescens</i> is a promising natural source of bioactive compounds for cosmetic applications, particularly in whitening and sun protection formulations.