Abstract | 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 E2 ( PGE2) 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 PGE2 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 PGE2 concentration was observed only in cells treated with rheinanthrone. Fifteen minutes after adding PGE2 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 PGE2; PGE2 acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells.
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Authors | Risako Kon, Nobutomo Ikarashi, Chika Nagoya, Tomoko Takayama, Yoshiki Kusunoki, Makoto Ishii, Harumi Ueda, Wataru Ochiai, Yoshiaki Machida, Kazuyuki Sugita, Kiyoshi Sugiyama |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 152
Issue 1
Pg. 190-200
(Feb 27 2014)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 24412547
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Anthracenes
- Laxatives
- Sennosides
- Aquaporin 3
- rhein-9-anthrone
- Senna Extract
- Dinoprostone
- Indomethacin
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Topics |
- Animals
- Anthracenes
(isolation & purification, pharmacology)
- Aquaporin 3
(metabolism)
- Cell Line
- Colon
(drug effects, metabolism)
- Colonic Neoplasms
(metabolism)
- Diarrhea
(chemically induced)
- Dinoprostone
(metabolism)
- HT29 Cells
- Humans
- Indomethacin
(pharmacology)
- Intestinal Mucosa
(drug effects, metabolism)
- Laxatives
(isolation & purification, pharmacology)
- Macrophage Activation
(drug effects)
- Male
- Rats
- Rats, Wistar
- Rheum
(chemistry)
- Senna Extract
(isolation & purification, pharmacology)
- Sennosides
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