Gastroprotective and ulcer-healing mechanisms of ellagic acid in experimental rats.

Ellagic acid (EA), a plant-derived polyphenol, exhibits antioxidant, anti-inflammatory, and gastroprotective effects. Its gastroprotective mechanisms have not been fully elucidated nor have its effects on chronic ulcer previously been described. Toward these ends, the antiulcer activities of EA were evaluated in acute (ethanol and indomethacin) and chronic (acetic acid) ulcer models in Wistar rats. In this study, oral administration of EA significantly prevented the gastric ulceration caused by ethanol, indomethacin, and acetic acid treatments. Its gastroprotective mechanism in ethanol-induced ulcer were partly due to intensification in the endogenous production of nitric oxide, an antioxidant effect by replenishing depletion of endogenous nonprotein sulfhydryls and attenuation of tumor necrosis factor-α increase, whereas in indomethacin ulcer, it is partly due to a reduction in the plasma level of leukotriene B(4). In acetic acid ulcer, promotion of ulcer-healing effects was partly due to attenuation of the elevated levels of the inflammatory cytokines TNF-α, interferon-γ, and interleukins-4 and -6. These findings suggest that ellagic acid exerts its antiulcer activity by strengthening the defensive factors and attenuating the offensive factors.