Inflammatory mediator regulation of the Zizyphus jujube leaf fractions in the LPS-stimulated Raw264.7 mouse machrophage

Abstract

Zizyphus jujube leaf fractions (ZLFs) showed no cytotoxic effects of up to 100 μg/mL, while the anti-inflammatory effects of ZLFs were analyzed by checking the productions of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), and inflammatory cytokines TNF-α, IL-1β, and IL-6 in the lipopolysaccharide (LPS)-stimulated Raw264.7 macrophage up to the concentration of 100 μg/mL. ZLFs (100 μg/mL) demonstrated a strong anti-inflammatory activity that reduced 61~85% of NO and 71~100% of PGE2 production in the LPS-stimulated Raw264.7 macrophage. Even the low ZLFs concentration of 1 μg/mL have reduced NO and PGE2 production by 34~64%. Expressions of COX-2 protein were also effectively inhibited by the ZLFs. Furthermore, the TNF-α, IL-1β, and IL-6 production were significantly suppressed through the treatment of ZLFs at concentrations of 1, 10, and 100 μg/mL. In the order of the Zizyphus jujube leaf water fraction (ZLWF) < buthanol fraction (ZLBF) < ethyl acetate fraction (ZLEF) showed anti-inflammatory activity. In particular, the ethyl acetate fraction ZLEF at 100 μg/mL showed an excellent anti-inflammatory activity by reducing the production of NO, PGE2, COX-2, and inflammatory cytokines (TNF-α, IL-1β, IL-6) in the level of Raw264.7 macrophage without LPS-stimulation or even better. The results of our study suggest the potential of ZLEF for use as an excellent ant-inflammatory inhibiting mediator and may be used as a therapeutic approach to various inflammatory diseases.