Anti-inflammatory and anti-melanogenic properties of active fucoidan JHCF4-e and its cosmetic applications.

In our previous study, we isolated an active fucoidan fraction (JHCF4) from Sargassum fusiforme. In this study, we compared the cellulase-assisted extract of JHCF4 (JHCF4-e) with the hot-water extract of JHCF4 (JHCF4-t) to evaluate their anti-inflammatory and anti-melanogenic activities. JHCF4-e exhibited higher fucose (63.86 %) and sulfate (17.27 % ± 0.09 %) contents, and demonstrated markedly stronger efficacy. In LPS-stimulated RAW 264.7 macrophages, JHCF4-e reduced nitric oxide (NO) levels to 42 % at 100 μg/mL, significantly suppressed iNOS and COX-2 expression, and downregulated MAPK phosphorylation together with PGE2, TNF-α, IL-1β, and IL-6 secretion. In zebrafish, JHCF4-e decreased neutrophil counts to 21.9 at 100 μg/mL compared with 49.6 for JHCF4-t, lowered NO fluorescence, and alleviated acetic acid-induced hyperactivity, confirming both anti-inflammatory and neuro-relieving effects. JHCF4-e also inhibited melanogenesis in B16-F10 cells by reducing melanin and tyrosinase activities (> 30 % at 100 μg/mL) and suppressing pigmentation in zebrafish larvae. A JHCF4-e-based formulation proved safe. Clinically, transepidermal water loss decreased by 69.7 % after 2 weeks (29.7 ± 11.3 to 9.0 ± 1.9 g/m2/h), hemoglobin levels were significantly reduced, and individual type angle (ITA°) values increased by 2.27 ± 4.38 at week 2, confirming barrier-protective, anti-inflammatory, and whitening efficacy. Collectively, these results demonstrate that enzyme-assisted extraction enhances fucoidan bioactivity and establish JHCF4-e as a promising multifunctional cosmetic ingredient, supported by cellular, animal, and human evidence.