| Project/Area Number |
11794037
|
|---|
| Research Category |
Grant-in-Aid for University and Society Collaboration
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Kyoto Pharmaceutical University |
|---|
Principal Investigator |
TAKEUCHI Koji Kyoto Pharmaceutical University, Professor, 薬学部, 教授 (00150798)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KATO Shinichi Kyoto Pharmaceutical University, Assistant Professor, 薬学部, 講師 (90281500)
SHIBATA Nobuhito Kyoto Pharmaceutical University, Associate Professor, 薬学部, 助教授 (60319449)
TAKADA Kanji Kyoto Pharmaceutical University, Professor, 薬学部, 教授 (30102106)
TANAKA Akiko Kyoto Pharmaceutical University, Research Assistant, 薬学部, 助手 (30329940)
YOSHIKAWA Yukako Kyoto Pharmaceutical University, Research Assistant, 薬学部, 助手 (30278444)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2001: ¥7,300,000 (Direct Cost: ¥7,300,000)
|
|---|
| Keywords | polyphenol / ellagic acid / ulcerative colitis / colonic delivery / microsphere capsule / protection / 炎症性病変 / モノクロラミン胃損傷 / 抗酸化作用 |
|---|
| Research Abstract |
Ellagic acid (EA), one of the polyphenols that are abundantly contained in whisky as a nonalcoholic component, has the antioxidant and anti-inflammatory activities. 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 : 1〜10mg/kg as EA contents) was administered p.o. twice daily for 6 days. These microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileocecal junction and distributed to the terminal ileum and the colon. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substances (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 10mg/kg, the ED_<50> being 2.3mg/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 ED_<50> 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.
|
