Ellagic acid (EA), a naturally occurring plant
phenol, has the
antioxidant and anti-inflammatory activities. In the present study, we examined the effect of EA contained in
microspheres on the
ulcerative colitis induced experimentally in rats by
dextran sulfate sodium (DSS). Experimental
colitis was induced in male Fisher 344 rats by daily treatment with 3% DSS
solution in
drinking water for 7 days. EA of
microspheres (mcEA: 1 approximately 10 mg/kg as EA contents) was administered p.o. twice daily for 6 days. In a preliminary study, we found that these
microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileo-cecal junction and distributed to the terminal ileum and the colon. The ulceration area, colon length, and mucosal
myeloperoxidase (MPO) activity as well as
thiobarbituric acid-reactive substances (
TBARS) were measured on 7th day after the onset of DSS treatment. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of MPO activity and
TBARS as well as the decreases of
body weight gain and colon length. Administration of mcEA reduced the severity of DSS-induced
colitis in a dose-dependent manner, and a significant effect was observed
at 10 mg/kg, the ED50 being 2.3 mg/kg. This mcEA treatment also significantly mitigated changes in various biochemical parameters in the colonic mucosa induced by DSS. Although plain EA (without using
microspheres) was also effective in reducing the severity of DSS-induced
colitis, this effect was much less potent as compared with that of mcEA; the ED50 was about 15 times higher than that of mcEA. In addition, a significant effect on DSS-induced
colitis was also obtained by intra-
rectal administration of
superoxide dismutase, an anti-oxidative agent. These results suggest that EA prevents the
ulcerative colitis induced by DSS, probably by radical scavenging and/or anti-oxidative actions. The
microspheres used in this study may be useful for delivering an orally administered drug specifically to the colon.