Low-molecular-weight ulvan prepared from the Korean seaweed Ulva pertusa enhances immune responses via signaling pathways, short chain fatty acids, and G-protein coupled receptors.

Ulvan isolated from Korean Ulva pertusa exhibits anti-inflammatory and immunomodulatory effects, and its structural properties have been characterized. In this study, low-molecular-weight ulvan (LMWU) was prepared and its immunostimulatory effects were investigated. Ulvan was fractionated by enzymatic degradation using ulvan lyase followed by size exclusion chromatography to obtain LMWU. Preliminary characterization revealed a fragmented structure including ulvan components. LMWU increased cytokine secretion and cytokine gene expression in macrophages. Additionally, LMWU stimulated the phagocytic activity of macrophages. These immune responses were likely initiated through TLR2 and TLR4, with MAPK and NF-κB pathways serving as the primary signaling mechanisms. Moreover, LMWU prevented weight loss and lymphoid tissue damage in cyclophosphamide (CTX)-induced immunosuppressed mice. LMWU administration restored the function of various immunocytes, including macrophages and NK, T, and B cells, after impairment by CTX. Changes in immunostimulatory cytokines and immunoglobulins were consistent with these findings. Interestingly, short-chain fatty acids and G-protein coupled receptors 41/43 were upregulated in cecal and colon tissues. These findings suggest that LMWU influences immune system activation through both direct and indirect mechanisms.