Neoagarotetraose from Marine Red Algae Ameliorates UVB-Induced Skin Barrier Damage in Mice and HaCaT Keratinocytes

Abstract

Ultraviolet B (UVB) radiation is a major environmental threat that disrupts skin integrity and drives inflammatory skin disorders. Neoagarotetraose (NA4), a low-molecular-weight oligosaccharide derived from marine red algae, is characterized by high bioavailability and well-documented anti-inflammatory properties, yet its role in UVB-induced skin damage remains unexplored. In this study, we investigated the reparative effects of NA4 and its underlying mechanisms using UVB-irradiated HaCaT keratinocytes and C57BL/6 mouse models, with focus on cytotoxicity, cell viability, barrier protein expression, pro-inflammatory cytokines, and MAPK pathway activation. Our results demonstrate that NA4 was non-cytotoxic and dose-dependently restored the viability of UVB-damaged keratinocytes. Notably, NA4 reestablished the expression of key barrier proteins (FLG, ZO-1, COL-I) and corrected UVB-induced elevation of aquaporin-3 (AQP3), while concurrently suppressing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and inhibiting the phosphorylation of JNK, ERK1/2, and p38 in both cell and animal models. In vivo, the 2 mg/cm² NA4 treatment achieved superior barrier restoration and anti-inflammatory effects compared to vitamin C. Collectively, these findings identify NA4 as a concentration-dependent, multi-target marine-derived oligosaccharide that concurrently exerts MAPK-mediated anti-inflammatory activity and barrier-restorative effects, offering a mechanistic basis for developing next-generation marine therapeutics against UVB-induced skin damage.