| Summary: | <i>Hibiscus syriacus</i> L. is distributed widely throughout Eastern and Southern Asia and considered as the national flower of South Korea. The extraction of several plant parts of <i>H. syriacus</i> L. is currently used as a natural remedy for several diseases, including breast and lung cancer, microbial infection, and chronic inflammation. However, the effect of the anthocyanin extract of <i>H. syriacus</i> L. petals (PS) in oxidative stress conditions has not been studied. In this study, we evaluated the cytoprotective effect of PS against H<sub>2</sub>O<sub>2</sub>-induced oxidative stress in HaCaT keratinocytes. In this study, we found that PS significantly inhibited H<sub>2</sub>O<sub>2</sub>-induced apoptosis of HaCaT keratinocytes. We also revealed that PS mediated-cytoprotective effect was associated with the increased expression of heme oxygenase-1 (HO-1) arising from the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PS also decreased H<sub>2</sub>O<sub>2</sub>-induced excessive intracellular ROS generation and restored H<sub>2</sub>O<sub>2</sub>-induced mitochondrial depolarization through the downregulation of mitochondrial ROS production. Furthermore, H<sub>2</sub>O<sub>2</sub>-induced Bax and caspase-3 expression was markedly abolished in the presence of PS. The inhibition of HO-1 by zinc protoporphyrin significantly attenuated the cytoprotective effect of PS in H<sub>2</sub>O<sub>2</sub>-treated HaCaT keratinocytes along with ROS generation, indicating that HO-1 crucially affects PS-mediated cytoprotective properties. Collectively, our results suggested that, under H<sub>2</sub>O<sub>2</sub>-mediated oxidative stress conditions, PS sustained a normal level of mitochondrial membrane potential and ROS generation in HaCaT keratinocytes by activating the Nrf2/HO-1 axis, exerting cytoprotective effects against oxidative stress.
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