Kohno H, Yoshitani S, Tsukio Y, Murakami A, Koshimizu K, Yano M, Tokuda H, Nishino H, Ohigashi H, Tanaka T
Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Life Sci. 2001 Jul 13;69(8):901-13. doi: 10.1016/s0024-3205(01)01169-9.
The modifying effects of dietary feeding of a polymethoxyflavonoid nobiletin isolated from Citrus unshiu on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of nobiletin on cell proliferation activity of ACF using a monoclonal antibody MIB-5. Rats were given subcutaneous injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce ACF. They also received the experimental diet containing 0.01% or 0.05% nobiletin for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 139 +/- 35 ACF/rat at the end of the study (week 5). Dietary administration of nobiletin caused significant reduction in the frequency of ACF: 70 +/- 15 (50% reduction, p<0.001) at a dose of 0.01% and 63 +/- 10 (55% reduction, p<0.001) at a dose of 0.05%. Nobiletin feeding significantly lowered MIB-5-index in ACF. Also, dietary administration of nobiletin significantly reduced prostaglandin E2 content in the colonic mucosa. These findings might suggest possible chemopreventive ability of nobiletin, through suppression of cell proliferating activity of ACF, in the development of ACF.
研究了从温州蜜柑中分离出的多甲氧基黄酮类化合物川陈皮素通过饮食喂养对雄性F344大鼠结肠中由氧化偶氮甲烷（AOM）诱导产生的异常隐窝病灶（ACF）的影响。我们还使用单克隆抗体MIB-5评估了川陈皮素对ACF细胞增殖活性的影响。大鼠每周皮下注射一次AOM（15毫克/千克体重），持续3周以诱导ACF。从首次注射AOM前一周开始，它们还接受了含0.01%或0.05%川陈皮素的实验性饮食，持续5周。在研究结束时（第5周），AOM暴露使每只大鼠产生139±35个ACF。饮食给予川陈皮素可使ACF的数量显著减少：0.01%剂量组为70±15个（减少50%，p<0.001），0.05%剂量组为63±10个（减少55%，p<0.001）。川陈皮素喂养显著降低了ACF中的MIB-5指数。此外，饮食给予川陈皮素显著降低了结肠黏膜中前列腺素E2的含量。这些发现可能表明川陈皮素在ACF的发生发展过程中，通过抑制ACF的细胞增殖活性，可能具有化学预防能力。
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