Abstract
Kawachi-bankan (Citrus maxima) is one of the citruses produced in Ehime, Japan. Although health functions of flavonoids and carotenoids in citrus peel have been studied very well, those of water-soluble substances in the peel have not been focused. We herein indicated the anti-inflammatory effect of Kawachi-bankan peel aqueous extract (KPE) in vitro and in vivo. KPE significantly inhibited the production of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α by LPS-stimulated RAW264.7 cells without cytotoxicity. KPE also significantly inhibited the mRNA expression levels of IL-6 and TNF-α in the cells, suggesting that KPE inhibits the production of inflammatory cytokines by suppressing the gene expression levels. Immunoblot analysis revealed that KPE shows an anti-inflammatory effect on macrophages through the suppression of the phosphorylation of p38 and the translocation of NF-κB into nucleus. The oral administration of KPE inhibited the serum levels of inflammatory cytokines and improved the survival rate in systemic inflammatory response syndrome (SIRS) model mice. Our experiments using a cell line suggested that KPE inhibits the production of inflammatory cytokines by macrophages in hyperinflammatory state. In addition, experiments in vivo showed that the oral administration of KPE inhibited the serum levels of inflammatory cytokines and improved the survival rate in SIRS model mice. Our findings indicated that KPE contributes to alleviating of a hyperinflammatory response.