Bletilla striata polysaccharide protects against UVA-induced skin damage by activating Nrf2/HO-1 signaling and inhibiting ferroptosis

Bletilla striata polysaccharide (BSP), a naturally derived glucomannan, has attracted increasing interest due to its excellent biocompatibility and diverse bioactivities. In this study, we investigated the potential of BSP as a photoprotective agent against ultraviolet A (UVA)-induced skin damage. Structural analysis confirmed that BSP is a linear β-(1 → 4)-glucomannan with a molecular weight of approximately 30.5 kDa, primarily composed of mannose and glucose units. In vitro, BSP treatment significantly improved the viability of UVA-irradiated keratinocytes. In vivo, BSP administration in a mouse model of UVA-induced photodamage effectively attenuated epidermal thickening, increased water content, and improved histological integrity. Mechanistically, BSP restored antioxidant capacity by activating the Nrf2/HO-1 signaling pathway and suppressed ferroptosis through upregulation of GPX4 and FTH1, reduction of lipid peroxidation and mitigation of iron accumulation. Multi-omics and immunofluorescence analyses further revealed cell type-specific responses and the central role of Nrf2 activation in mediating BSP's protective effects. Collectively, these findings highlight BSP as a promising natural polysaccharide for preventing UVA-induced oxidative skin damage and advancing the development of functional biomaterials for photoprotection.