The Application of Resveratrol Derivatives in Oral Cells Reduces the Oxidative Stress Induced by Glucocorticoids

Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound healing. Resveratrol (RSV) is known for its antioxidant properties, but its limited bioavailability hinders its clinical use. This study investigated the potential of two RSV derivatives (<b>1d</b> and <b>1h</b>) to address these limitations. The antioxidant abilities of <b>1d</b> and <b>1h</b> (5 μM) against DEX-induced oxidative stress (200 μM) were evaluated in human gingival fibroblasts (hGFs) and osteoblasts (hOBs). The effects of these compounds on cell viability, morphology, ROS levels, SOD activity, gene expression, and collagen production were evaluated. RSV derivatives, under DEX-induced oxidative stress condition, improved cell growth at 72 h (191.70 ± 10.92% for <b>1d</b>+DEX and 184.80 ± 13.87% for <b>1h</b>+DEX), morphology, and SOD activity (77.33 ± 3.35 OD for <b>1d</b>+DEX; 76.87 ± 3.59 OD for <b>1h</b>+DEX at 1 h), while reducing ROS levels (2417.33 ± 345.49 RFU for <b>1d</b>+DEX and 1843.00 ± 98.53 RFU at 4 h), especially in hOBs. The co-treatment of RSV or derivatives with DEX restored the expression of genes that were downregulated by DEX, such as HO-1 (1.76 ± 0.05 for <b>1d</b>+DEX and 1.79 ± 0.01 for <b>1h</b>+DEX), CAT (0.97 ± 0.06 for <b>1d</b>+DEX and 0.99 ± 0.03 for <b>1h</b>+DEX), NRF2 (1.62 ± 0.04 for <b>1d</b>+DEX and 1.91 ± 0.05 for <b>1h</b>+DEX), SOD1 (1.63 ± 0.15 for <b>1d</b>+DEX and 1.69 ± 0.04 for <b>1h</b>+DEX). In addition, <b>1d</b> and <b>1h</b> preserved collagen production (111.79 ± 1.56 for <b>1d</b>+DEX and 122.27 ± 1.56 for <b>1h</b>+DEX). In conclusion, this study suggests that the RSV derivatives <b>1d</b> and <b>1h</b> hold promise as potential antioxidant agents to counteract DEX-induced oxidative stress. These findings contribute to the development of novel therapeutic strategies for managing oxidative stress-related oral conditions.