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Molecular mechanisms of immunomodulatory activity by polysaccharide isolated from the peels of Citrus unshiu.

M. Shin,Su beom Park,K. Shin

Published 2018 in International Journal of Biological Macromolecules

ABSTRACT

The extracts of the Citrus unshiu fruit induce numerous biological activities such as anticancer, anti-adipogenic, and antimicrobial effects. Furthermore, its peel has been used as a Chinese medicine for centuries and is consumed as a tea in China, Japan, and Korea. We investigated the effects of the polysaccharide isolated from C. unshiu peel (CPE-II) on cytokine and inflammatory mediator production in RAW 264.7 macrophages and performed signal transduction experiments to identify the pathways involved in its actions. CPE-II exhibited macrophage-stimulatory activity by inducing the production of interleukin (IL)-6, tumor necrosis factor (TNF)-α and nitric oxide (NO) in RAW 264.7 macrophages. Signal transduction experiments showed that CPE-II phosphorylated mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in RAW 264.7 cells in a concentration-dependent manner. The effects of CPE-II on IL-6/IL-12 and TNF-α production were completely suppressed by a specific inhibitor of c-Jun N-terminal kinase (JNK). Moreover, experiments with neutralizing antibodies showed that Toll-like receptor 2 (TLR2) and TLR4 were involved in the stimulation of IL-6 and NO production by CPE-II in RAW 264.7 cells. Collectively, these results suggest that the TLR2/4 and JNK pathways are essential for the CPE-II immune activity in RAW 264.7 cells.

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