Protective Effect of Polysaccharide P2 from Sargassum Fusiforme on Photoaging in HaCaT Cells and Its Mechanism via the TGF-β/SMAD Signaling Pathway

Skin photoaging is primarily induced by ultraviolet B (UVB) radiation and is characterized by extracellular matrix (ECM) degradation and chronic inflammation. To investigate the anti-photoaging activity of polysaccharide P2 derived from Sargassum fusiforme and its underlying molecular mechanisms, this study established a UVB-induced photoaging model in HaCaT cells. The results demonstrated that polysaccharide P2 significantly ameliorated UVB-induced cellular morphological damage. At the protein level, P2 at a concentration of 0.500 mg/mL significantly inhibited the secretion of MMP-1, MMP-3, and MMP-9, with inhibition rates reaching 46.72%, 53.52%, and 56.48%, respectively. Concurrently, it promoted the secretion of TIMP-1 (an inhibitor of the aforementioned MMPs) and the key growth factor TGF-β1, while reducing the levels of the pro-inflammatory cytokines IL-6 and TNF-α. At the gene level, P2 upregulated COL1α1 expression (up to 5.80-fold compared with the model group) and downregulated the transcription of MMP-1, MMP-3, MMP-9, and the inflammatory genes IL-6 and TNF-α. Mechanistic studies reveal that P2 activates the UVB-suppressed TGF-β/SMAD signaling pathway, significantly upregulating the expression of TGF-β1, TβR-I, TβR-Ⅱ, and the downstream SMAD2, SMAD3 and SMAD4, while simultaneously suppressing the expression of SMAD7 and the downstream effector genes c-JUN and c-FOS. Upon blockade of this pathway using the specific inhibitor LY2109761, the collagen-promoting effect of P2 was abolished, and its inhibitory efficiency against MMP-1, MMP-3, and MMP-9 was markedly diminished. For instance, the inhibition rate of P2 against MMP-1 dropped from 41.18% to 13.81%. Conversely, in cells overexpressing TGF-β1, the anti-photoaging effect of P2 was further enhanced. In conclusion, this study systematically elucidates the molecular mechanism by which polysaccharide P2 from Sargassum fusiforme effectively counteracts skin photoaging through targeted activation of the TGF-β/SMAD signaling pathway, leading to coordinated regulation of ECM metabolism and inflammatory responses. These findings provide a solid theoretical foundation for its development as a natural anti-photoaging agent.