Antioxidant Active Phytochemicals in Ternstroemia lineata Explained by Aquaporin Mechanisms

The antioxidant action of terngymnoside C (<b>1</b>) and hydroxytyrosol-1-glucoside (<b>2</b>), isolated for the first time from the flower buds of <i>Ternstroemia lineata</i>, as well as katsumadin (<b>3</b>), obtained from the seedless fruits, was evaluated using ABTS^•+ and H₂O₂-<i>Saccharomyces cerevisiae</i> models. In silico docking analysis of <b>1</b>, <b>2</b>, and <b>3</b> determined their affinity forces to the aquaporin monomers of the modeled <i>S. cerevisiae</i> protein 3 (AQP3) and human protein 7 (AQP7) channels that regulate the H₂O₂ cell transport. The ABTS^•+ antiradical capacity of these compounds showed IC₅₀ values of 22.00 μM (<b>1</b>), 47.64 μM (<b>2</b>), and 73.93 μM (<b>3</b>). The <i>S. cerevisiae</i> antioxidant assay showed that at 25 µM (<b>1</b>) and 50 µM (<b>2</b> and <b>3</b>), the cells were protected from H₂O₂-oxidative stress. These compounds, together with quercetin and vitamin C, were explored through the modeled <i>S. cerevisiae</i> AQP3 and human AQP7 by molecular docking analysis. To explain these results, an antioxidant mechanism for the isolated compounds was proposed through blocking H₂O₂ passage mediated by aquaporin transport. On the other hand, <b>1</b>, <b>2,</b> and <b>3</b> were not cytotoxic in a panel of three cancer cell lines.