| Summary: | <i>Alpinia oxyphylla</i> Miquel (Zingiberaceae) has been reported to show antioxidant, anti-inflammatory, and neuroprotective effects. In this study, two new eudesmane sesquiterpenes, 7α-hydroperoxy eudesma-3,11-diene-2-one (<b>1</b>) and 7β-hydroperoxy eudesma-3,11-diene-2-one (<b>2</b>), and a new eremophilane sesquiterpene, 3α-hydroxynootkatone (<b>3</b>), were isolated from the MeOH extract of dried fruits of <i>A. oxyphylla</i> along with eleven known sesquiterpenes (<b>4</b>–<b>14</b>). The structures were elucidated by the analysis of 1D/2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and optical rotation data. Compounds (<b>1</b>–<b>3</b>, <b>5</b>–<b>14</b>) were evaluated for their protective effects against <i>tert</i>-butyl hydroperoxide (tBHP)-induced oxidative stress in adipose-derived mesenchymal stem cells (ADMSCs). As a result, treatment with isolated compounds, especially compounds <b>11</b> and <b>12,</b> effectively reverted the damage of tBHP on ADMSCs in a dose-dependent manner. In particular, <b>11</b> and <b>12</b> at 50 µM improved the viability of tBHP-toxified ADMSCs by 1.69 ± 0.05-fold and 1.61 ± 0.03-fold, respectively.
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