Anti-inflammatory effects of black rice, cyanidin-3-O-β-d-glycoside, and its metabolites, cyanidin and protocatechuic acid

The anti-inflammatory effects of cyanidin-3-O-β-d-glycoside (C3G), a major constituent of black rice (BR), and its metabolites, cyanidin and protocatechuic acid (PA), were assessed in lipopolysaccharide (LPS)-induced RAW 264.7 cells and carrageenan-induced inflammation in air pouches in BALB/c mice. BR, C3G and its metabolites suppressed the production of the proinflammatory cytokines, TNF-α and IL-1β, and the inflammatory mediators, NO and prostaglandin E2 (PGE₂), as well as the gene expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. These agents also inhibited the phosphorylation of IκB-α, the nuclear translocation of NF-κB, and the activation of mitogen-activated protein kinases. Furthermore, these agents significantly inhibited the leukocyte number and the levels of TNF-α, PGE₂, and protein in the exudates of the air pouch in carrageenan-treated mice, as well as COX-2 expression and NF-κB activation. Among the test agents, PA most potently inhibited these inflammatory mediators in vivo and in vitro. Based on these findings, if BR is orally administered, its main constituent, C3G, may be metabolized to cyanidin and/or PA, which express potent anti-inflammatory effects by regulating NF-κB and MAPK activation.