*Article* **E** ff**ect of Manitoba-Grown Red-Osier Dogwood Extracts on Recovering Caco-2 Cells from H 2 O 2-Induced Oxidative Damage**

**Runqiang Yang 1,2, Qianru Hui 2, Qian Jiang 2, Shangxi Liu 2, Hua Zhang 3, Jiandong Wu 4, Francis Lin 4, Karmin O 2,5 and Chengbo Yang 2,\***


Received: 27 June 2019; Accepted: 26 July 2019; Published: 28 July 2019

**Abstract:** Red-osier dogwood, a native species of flowering plant in North America, has been reported to have anti-oxidative properties because of abundant phenolic compounds; this could be promising as a functional food or a feed additive. In the present study, an oxidative damage model using 1.0 mM hydrogen peroxide (H2O2) in Caco-2 cells was established to evaluate the antioxidative effects of red-osier dogwood extracts (RDE). The results showed that 1.0 mM H2O2 pre-exposure for 3 h significantly decreased cell viability, and increased interleukin 8 (IL-8) secretion and the intracellular reactive oxygen species (ROS) level. Caco-2 cells were treated with 100 μg/mL RDE for 24 h after pre-exposure to H2O2. It was found that the decreased cell viability caused by H2O2 was significantly restored by a subsequent 100 μg/mL RDE treatment. Furthermore, the IL-8 secretion and ROS level were significantly blocked by RDE, accompanied by the enhanced gene expression of hemeoxygenase-1 (HO-1), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and the enhanced protein expression of the nuclear factor (erythroid-derived 2)-like 2 (Nrf-2). Moreover, RDE improved barrier functions in Caco-2 cells. Using RDE reduced the di ffusion of fluorescein isothiocyanate (FITC)-dextran and increased the transepithelial resistance (TEER) value. The relative mRNA level of tight junction claudin-1, claudin-3, and occludin was elevated by RDE. These extracts also repaired the integrity of zonula occludens-1 (ZO-1) damaged by H2O2 and increased the protein expressions of ZO-1 and claudin-3 in the H2O2-pretreated cells. These results illustrated that RDE reduced the ROS level and enhanced the barrier function in oxidative-damaged epithelial cells.

**Keywords:** red-osier dogwood; antioxidative e ffect; H2O2; transepithelial resistance (TEER); Caco-2 cells
