The Cytoprotective Effects of Baicalein on H(2)O(2)-Induced ROS by Maintaining Mitochondrial Homeostasis and Cellular Tight Junction in HaCaT Keratinocytes

Reactive oxygen species (ROS) promote oxidative stress, which directly causes molecular damage and disrupts cellular homeostasis, leading to skin aging. Baicalein, a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi has antioxidant, anticancer, anti-inflammatory, and other medicinal properties. We aimed to investigate the protective effect of baicalein on the disruption of tight junctions and mitochondrial dysfunction caused by H(2)O(2)-induced oxidative stress in HaCaT keratinocytes. The cells were pretreated with 20 and 40 µM baicalein followed by treatment with 500 µM H(2)O(2). The results revealed that baicalein exerted antioxidant effects by reducing intracellular ROS production. Baicalein attenuated the degradation of the ECM (MMP-1 and Col1A1) and the disruption of tight junctions (ZO-1, occludin, and claudin-4). In addition, baicalein prevented mitochondrial dysfunction (PGC-1 [Formula: see text] , PINK1, and Parkin) and restored mitochondrial respiration. Furthermore, baicalein regulated the expression of antioxidant enzymes, including NQO-1 and HO-1, via the Nrf2 signaling pathway. Our data suggest that the cytoprotective effects of baicalein against H(2)O(2)-induced oxidative stress may be mediated through the Nrf2/NQO-1/HO-1 signaling pathway. In conclusion, baicalein exerts potent antioxidant effects against H(2)O(2)-induced oxidative stress in HaCaT keratinocytes by maintaining mitochondrial homeostasis and cellular tight junctions.