Shikonofuran E plays an anti-inflammatory role by down-regulating MAPK and NF-κB signaling pathways in lipopolysaccharide-stimulated RAW264.7 macrophages.

The anti-inflammatory effects of shikonofuran E from Onosma paniculatum on RAW 264.7 murine macrophage cells induced by lipopolysaccharide (LPS) were first time examined. A series of non-cytotoxic concentrations of shikonofuran E (< 10 μM) treatments were found to reduce the accumulation of pro-inflammatory cytokine, including tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-1β (IL-1β), and inhibit the expression of nitric oxide synthase (iNOS) and cyclooxidase-2 (COX-2) in the LPS-stimulated macrophages as compared to the LPS-only treated cells. Nitric oxide (NO) production was also significantly suppressed in a dose-dependent manner (P < 0.05) with an IC50, the phosphorylation level of JNK of 3.5 µg/mL. In the anti-inflammatory pathway studies, ERK, p38 and IκBα were also decreased by shikonofuran E at 10 μM, in spite of the total levels of the MAPK isoforms and IκBα did not differ significantly. Our results indicate that shikonofuran E could exert an anti-inflammatory effect on LPS-induced RAW264.7 cells by down-regulating MAPK and NF-κB signaling pathways and regulating a series of cytokine production in lipopolysaccharide-stimulated RAW264.7 macrophages.