Protective effect of polysaccharide from <em>Sargassum fusiforme</em> against UVB-induced skin barrier damage in HaCaT cells and BALB/c hairless mice

Excessive ultraviolet B (UVB) exposure disrupt the skin barrier, provoking inflammation. This study investigated the protective effects of a degraded <em>Sargassum fusiforme </em>polysaccharide (DSFP-45) against UVB-induced barrier dysfunction in HaCaT keratinocytes and BALB/c nude mice. DSFP-45 significantly improved cell viability, reduced reactive oxygen species, and restored barrier-protiens (filaggrin, loricrin, and aquaporin 3) in UVB-irradiated HaCaT cells. It suppressed pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) by inhibiting the PI3K/Akt/NF-κB pathway. <em>In vivo</em>, oral and topical DSFP-45 alleviated erythema, reduced transepidermal water loss, preserved collagen and elastic fibers, normalized ceramide levels, and suppressed pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). The 16s rRNA sequencing showed that DSFP-45 increased beneficial skin microbiota (<em>Staphylococcus</em> and <em>Lactobacillus</em>), and reduced harmful taxa (<em>Corynebacterium</em>, <em>Streptococcus</em>, and <em>Stenotrophomonas</em>). Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis showed that the skin microbiota under DSFP-45 treatment influence biosynthesis of amino acids and biosynthesis of secondary metabolites. These findings demonstrate that DSFP-45 protected against UVB-induced skin barrier damage by enhancing barrier protein expression, dampening inflammation, and possibly by modulating skin microbiota, supporting its potential as a natural anti-photodamage agent.