Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract
Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract
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DOI：
10.1016/j.jep.2013.12.055
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发表时间：
2014-02-27
影响因子：
5.4
通讯作者：
Sugiyama, Kiyoshi
中科院分区：
文献类型：
--
作者：
Kon, Risako;Ikarashi, Nobutomo;Sugiyama, Kiyoshi
民族药理学相关性：水通道蛋白-3（AQP 3）在结肠粘膜上皮细胞中表达，对调节粪便含水量很重要。方法：大鼠灌胃大黄提取物及其主要成分番泻苷A后，检测其对粪便含水量、结肠AQP 3表达和前列腺素E2（PGE 2）浓度的影响。结果：大黄提取物致泻过程中，结肠组织中PGE（2）水平升高，而AQP 3表达显著降低。当给予番泻苷A时也观察到类似的变化。当番泻苷A或其代谢产物大黄蒽酮和大黄酸加入Raw 264.7细胞中时，仅在大黄蒽酮处理的细胞中观察到PGE（2）浓度的显著增加。在HT-29细胞中加入PGE（2）15分钟后，AQP 3表达下降至对照组的约40%。结论：番泻苷A可能通过降低结肠AQP 3的表达，抑制水从肠腔向血管侧的转运，从而发挥通便作用。AQP 3水平的降低是由番泻苷A的代谢产物大黄蒽酮引起的，该代谢产物激活结肠中的巨噬细胞并增加PGE（2）的分泌; PGE（2）作为旁分泌因子并降低结肠粘膜上皮细胞中AQP 3的表达。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Aquaporin-3 (AQP3) is expressed in mucosal epithelial cells in the colon and is important for regulating fecal water content. We examined the role of AQP3 in the laxative effect of rhubarb extract.Methods: After orally administering rhubarb extract or its major component (sennoside A) to rats, the fecal water content, AQP3 expression and prostaglandin E-2 (PGE(2)) concentrations in the colon were examined. The mechanism by which sennoside A decreases the expression of AQP3 was examined using the human colon cancer HT-29 cells and macrophage-derived Raw264.7 cells.Results: During diarrhea by rhubarb extract administration, the PGE(2) levels in the colon increased while the AQP3 expression significantly decreased. Similar changes were also observed when sennoside A was administered. When sennoside A or its metabolites, rheinanthrone and rhein were added to Raw264.7 cells, a significant increase in the PGE(2) concentration was observed only in cells treated with rheinanthrone. Fifteen minutes after adding PGE(2) to the HT-29 cells, the AQP3 expression decreased to approximately 40% of the control. When pretreated-with indomethacin, sennoside A neither decreased the AQP3 expression nor induced diarrhea.Conclusions: Sennoside A may decrease AQP3 expression in the colon to inhibit water transport from the luminal to the vascular side, leading to a laxative effect. The decreases in the levels of AQP3 are caused by rheinanthrone, which is a metabolite of sennoside A, this metabolite activates the macrophages in the colon and increases the secretion of PGE(2); PGE(2) acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.