Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, USA.
J Agric Food Chem. 2010 Apr 14;58(7):3965-9. doi: 10.1021/jf902857v.
Recent data suggest that ellagitannins (ETs), a class of hydrolyzable tannins found in some fruits and nuts, may have beneficial effects against colon cancer. In the stomach and gut, ETs hydrolyze to release ellagic acid (EA) and are converted by gut microbiota to urolithin A (UA; 3,8-dihydroxy-6H-dibenzopyran-6-one) type metabolites, which may persist in the colon through enterohepatic circulation. However, little is known about the mechanisms of action of either the native compounds or their metabolites on colon carcinogenesis. Components of Wnt signaling pathways are known to play a pivotal role in human colon carcinogenesis, and inappropriate activation of the signaling cascade is observed in 90% of colorectal cancers. This study investigated the effects of UA, EA, and ET-rich fruit extracts on Wnt signaling in a human 293T cell line using a luciferase reporter of canonical Wnt pathway-mediated transcriptional activation. The ET extracts were obtained from strawberry (Fragaria annassa), Jamun berry (Eugenia jambolana), and pomegranate (Punica granatum) fruit and were all standardized to phenolic content (as gallic acid equivalents, GAEs, by the Folin-Ciocalteu method) and to EA content (by high-performance liquid chromatography methods): strawberry = 20.5% GAE, 5.0% EA; Jamun berry = 20.5% GAE, 4.2% EA; pomegranate = 55% GAE, 3.5% EA. The ET extracts (IC(50) = 28.0-30.0 microg/mL), EA (IC(50) = 19.0 microg/mL; 63 microM), and UA (IC(50) = 9.0 microg/mL; 39 microM) inhibited Wnt signaling, suggesting that ET-rich foods have potential against colon carcinogenesis and that urolithins are relevant bioactive constituents in the colon.
最近的数据表明，鞣花单宁（ETs），一类存在于某些水果和坚果中的可水解单宁，可能对结肠癌有有益的影响。在胃和肠道中，ETs 水解释放鞣花酸（EA），并被肠道微生物群转化为尿石素 A（UA；3,8-二羟基-6H-二苯并吡喃-6-酮）型代谢物，这些代谢物可能通过肠肝循环在结肠中持续存在。然而，对于天然化合物或其代谢物对结肠癌发生的作用机制知之甚少。Wnt 信号通路的成分已知在人类结肠癌发生中发挥关键作用，并且在 90%的结直肠癌中观察到信号级联的不适当激活。本研究使用经典 Wnt 途径介导的转录激活的荧光素酶报告基因，在人 293T 细胞系中研究了 UA、EA 和富含 ET 的水果提取物对 Wnt 信号的影响。ET 提取物从草莓（ Fragaria annassa ）、 Jamun 浆果（ Eugenia jambolana ）和石榴（ Punica granatum ）中获得，并均按酚含量（以福林-考尔法特法测定的没食子酸当量，GAEs）和 EA 含量（高效液相色谱法）标准化：草莓=20.5%GAE，5.0%EA； Jamun 浆果=20.5%GAE，4.2%EA；石榴=55%GAE，3.5%EA。ET 提取物（IC50=28.0-30.0μg/mL）、EA（IC50=19.0μg/mL；63μM）和 UA（IC50=9.0μg/mL；39μM）抑制了 Wnt 信号，这表明富含 ET 的食物具有预防结肠癌发生的潜力，而尿石素是结肠中相关的生物活性成分。
