期刊
JOURNAL OF ETHNOPHARMACOLOGY
卷 152, 期 1, 页码 190-200出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2013.12.055
关键词
Aquaporin-3; Sennoside A; Laxative; PGE(2); Macrophage; Rheinanthrone
资金
- Japan Society for the Promotion of Science [23790306]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [25860195, 24590136, 23790306] Funding Source: KAKEN
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.
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