Protective Responses of Green Yuja Peel Extracts to Lipopolysaccharide-Induced Inflammation and Reactive Oxygen Species Production in RAW264.7 Cells

This study assessed the anti-inflammatory and antioxidant effects of green yuja peel hot water extract (GYW) and ethanol extract (GYE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. GYW and GYE (50, 100, and 200 mu g/mL) significantly reduced the LPS-induced production of nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor- a (TNF-a), and reactive oxygen species in a concentration-dependent manner, without cytotoxicity. Compared with control cells, GYW and GYE significantly downregulated the protein levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) and the gene expression of iNOS, , COX-2 , TNF-a,- a , and IL-6 . Conversely, they upregulated the gene expression of IL-10. . Moreover, GYW and GYE significantly suppressed NF-KB p65 and IKB-a phosphorylation and increased the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1) compared with control cells. These results suggest that GYW and GYE exhibit anti-inflammatory and antioxidative properties by downregulating the NF-KB signaling pathway and upregulating the Nrf2/HO-1 system in LPS-activated macrophages.