Protective effects and mechanism of hydroxylpurpurin on H₂O₂-induced oxidative stress injury in skin

<title>Abstract</title> The skin serves as the primary barrier protecting the body from environmental insults and is highly susceptible to oxidative stress induced by excessive production of reactive oxygen species (ROS), which contributes to skin aging and inflammatory skin disorders. The endocannabinoid system (ECS) plays a critical role in regulating skin inflammation and oxidative stress; however, natural compounds targeting this system remain largely unexplored. Hydroxylpurpurin, a natural anthraquinone compound isolated from Rubia cordifolia L., exhibits potent antioxidant activity, but its protective mechanism against skin oxidative stress has not been fully elucidated.In this study, an integrated strategy combining network pharmacology, molecular docking, and experimental validation was employed to investigate the molecular mechanisms underlying the antioxidant effects of hydroxylpurpurin. Network pharmacology analysis and Molecular docking revealed that the potential targets of hydroxylpurpurin associated with skin oxidative stress were significantly enriched in the PI3K/AKT signaling pathway, suggesting its pivotal involvement in the protective effects of hydroxylpurpurin. Moreover, experimental validation using an oxidative stress model in HaCaT keratinocytes showed that hydroxylpurpurin markedly reduced intracellular ROS levels and alleviated oxidative stress-induced cellular damage. Collectively, these findings indicate that hydroxylpurpurin may exert its antioxidant effects by modulating ECS-related targets and activating the PI3K/AKT signaling pathway, providing novel insights into its potential application for the prevention and treatment of skin oxidative stress-related disorders.