The potential immunomodulatory mechanism of fucoidan, a heteropolysaccharide from Sargassum hemiphyllum through TNF and IL-17 signaling pathways based on RNA-seq

The crude fucoidan extracted from Sargassum hemiphyllum (S. hemiphyllum) demonstrated notable immunomodulatory effects; however, its structural features and mechanistic underpinnings remained poorly understood. In this study, the crude polysaccharide from S. hemiphyllum (F) was purified to yield a product named FS, its molecular characteristics, thermal properties, and microscopic morphology were systematically examined, alongside its immunomodulatory mechanisms. The main monosaccharide components of F were fucose (22.80%), galactose (15.40%), glucuronic acid (15.95%), and mannuronic acid (14.40%), while FS were primarily composed of fucose (23.00%), mannose (13.39%), xylose (12.36%) and glucuronic acid (24.24%). All three polysaccharides exhibited favorable thermal stability. Immunostimulation assays indicated that FS significantly promoted the secretion of cytokines—TNF-α, IL-1β, and IL-6 in RAW264.7 macrophages. RNA sequencing analysis further identified 501 differentially expressed genes after FS treatment, comprising 206 up-regulated and 295 down-regulated genes. Mechanistic studies revealed that FS mediates immunomodulation mainly via activation of the TNF/IL-17 signaling pathway. These findings offer new perspectives on the immunomodulatory mechanisms of marine polysaccharides and provide a critical theoretical foundation for their application in functional foods and nutritional supplements.