Undaria pinnatifida Fucoidan-Rich Extract Induces Both Innate and Adaptive Immune Responses

Abstract

Fucoidans are widely used as an ingredient of dietary supplements. We investigated the immune stimulatory activities of Undaria pinnatifida (Alariaceae) fucoidan-rich extract (UPF-RE) in vitro as well as in vivo. In vitro, the extract stimulated Raw 264.7 cells to produce significant nitric oxide (NO) metabolites and cytokines (TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6). It also induced the proliferation of primary mouse splenocytes and the secretion of IL-4, which correlated with the phosphorylation of Extracellular-signal-regulated kinase (ERK) protein. In in vivo experiments, first, 50 mg/kg of 3 different types of UPF-RE, DSU02, DSU02L (low molecular weight, <3 kDa), and DSU02H (high molecular weight, >10 kDa), were orally administered to C57BL/6 mice. After 14 days, the frequencies of CD3+, CD4+, and CD8+ T cells and NK cells from each group were analyzed. Plasma concentrations of TNF-alpha and IFN-gamma were determined. The frequencies of CD3+ and CD4+ showed a statistically significant increase in splenocytes isolated from the DSU02 and DSU02H groups. Also, there was significant production of TNF-alpha and IFN-gamma from the DSU02 group. Second, 3 different concentrations of DSU02 (50, 100, and 150 mg/kg) were orally administered. After 14 days, the proliferative capacity of CD3+, CD4+, and CD8+ T cells was investigated, and the plasma concentrations of IgM and total IgG were determined. Plasma concentration of IgM from the DSU02 150 mg/kg group was statistically significantly higher compared with that from the other groups. We suggest that UPF-RE could be a good candidate for a natural immune stimulator to induce innate as well as adaptive immune responses.