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Ellagic Acid Protects Against LPS-Induced Acute Lung Injury Through Inhibition of Nuclear Factor Kappa B, Proinflammatory Cytokines and Enhancement of Interleukin-10

Abstract

Ellagic acid is a naturally occurring polyphenolic compound which is found in many fruits, nut galls and plant extracts. In the present study, we explored the ability of ellagic acid to modulate LPS response using macrophage-mediated inflammatory conditions and acute lung injury (ALI). Methods and Results: First, we found that ellagic acid reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin- 1β (IL-1β) secretions, enhance interleukin-6 (IL-10) production by lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro. These results inspired us to further study the effects of ellagic acid in vivo. In murine ALI model, mice were treated with ellagic acid prior to LPS challenge. The data showed that ellagic acid possess a protective effect on LPS-induced ALI in mice. In addition, We further investigated how ellagic acid worked on signal transduction by western-blot and immunocytochemical analysis. The data showed that ellagic acid efficiently blunted nuclear factor-kappa B (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα, as well as the translocation of p65 from cytoplasm to the nucleus. Conclusions: These results indicate that ellagic acid could be highly effective in inhibiting ALI, and underlying mechanism may be through shocking the NF-κB pathway to attenuate the nonspecific pulmonary inflammation induced by LPS administration.

Shuang Guan, Zhe Feng, Sitong Ma, Yujia Wang, Bo Sun, Wanlu Li, Bing Han and Jing Lu

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