Protection against dextran sulfate sodium-induced colitis by microsheres of polyphenol (ellagic acid)

鞣花酸（EA）是威士忌中含量丰富的多酚类物质之一，具有抗氧化和抗炎作用。本研究观察了EA微球对葡聚糖硫酸钠（DSS）诱导的大鼠溃疡性结肠炎的治疗作用。在雄性Fisher 344大鼠中通过每天用3%DSS饮用水溶液处理7天来诱导实验性结肠炎。微球EA（mcEA：1 × 10 mg/kg EA含量）经口给药。每日两次，共6天。这些微球胶囊，当口服给药时，在回盲部近端有效溶解并分布到末端回肠和结肠。DSS处理7 d后，结肠粘膜损伤严重，髓过氧化物酶（MPO）活性和硫代巴比妥酸反应物质（TBARS）含量增加，体重增加和结肠长度减少。mcEA剂量依赖性地减轻DSS诱导的结肠炎的严重程度，在10 mg/kg时观察到显著效果，艾德_<50>为2.3mg/kg。这种mcEA治疗还显著减轻了DSS诱导的结肠粘膜中各种生化参数的变化。虽然普通EA（不使用微球）也能有效降低DSS诱导的结肠炎的严重程度，但与mcEA相比，这种效果要弱得多;艾德_<50>比mcEA高约15倍。此外，通过直肠内给予超氧化物歧化酶（一种抗氧化剂），也对DSS诱导的结肠炎产生了显著影响。这些结果表明，EA预防DSS诱导的溃疡性结肠炎，可能是通过清除自由基和/或抗氧化作用。在这项研究中使用的微球可能是有用的，用于提供口服给药的药物，特别是结肠。

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.