Inflammation is the body’s way of dealing with tissue damage, infection or irritants and can be initiated by non-specific and specific immune reaction. Inflammation is a local response which limits damage caused by injury to a local site and results in redness, swelling, heat and pain. There is a fine balance between the beneficial effects of inflammation cascades and their potential for long-term tissue destruction. If they are not controlled or resolved, inflammation cascades can lead to the development of diseases such as chronic asthma, rheumatoid arthritis, cardiovascular disease and certain types of cancer. During many inflammation-associated pathologies, nitric oxide (NO) production increases significantly. NO has a variety of biological activities including vasodilation, neurotransmission and cytotoxicity. The free radical nature of NO and the high reactivity with superoxide renders NO a potent pro-oxidant molecule which is able to induce oxidative damage and potentially harmful toward cellular targets. Owing to the importance of the control of NO production for human health, the attention of many research groups has been focused on the mechanisms responsible of the reversal of NO effects from protective to deleterious. Ellagic acid (EA) is a naturally occurring plant polyphenol. EA has been shown to possess numerous anticarcinogenic and antimutagenic properties towards a variety of different carcinogens. In addition, EA also has potent antioxidant properties in vivo and in vitro. Expanding upon from current understanding, we examined the effects of EA on lipopolysaccharide (LPS)-induced of nitric oxide (NO), tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）productions using macrophage RAW264.7 cells and revealed the possible mechanisms underlying. The results indicate that EA inhibited LPS-induced NO production in a dose-dependent manner. Furthermore, EA also decreased the levels of IL-6 and TNF-α. In the presence of EA, inducible nitric oxide synthase（iNOS）protein and mRNA levels were declined significantly as compared with LPS induction alone. Both IκB and NF-κB expressions were also increased with the supplementation of EA. These findings implicate that EA can be applied in the regulation of macrophage-mediated inflammatory diseases.
