Downregulation of aquaporin 3 mediated the laxative effect in the rat colon by a purified resin glycoside fraction from pharbitis semen

Abstract

Background. Pharbitis Semen, the seeds of Pharbitis nil, is widely used as a traditional purgative medicine in China, Korea, and Japan. This study investigated the laxative effects of a purified resin glycoside fraction obtained in our previous study from Pharbitis Semen in vivo and in vitro. Materials and Methods. After orally administering a purified resin glycoside fraction from Pharbitis Semen (RFP) to rats, the content of fecal water, AQP3, NF-B, COX-2 expression, and the prostaglandin E 2 (PGE 2 ) concentrations in the colon were examined. Moreover, human intestinal epithelial cells (HT-29) were used to investigate the mechanism of RFP decreasing the AQP3 expression. Results. Results obtained showed that treatment with RFP increased the feces excretion and fecal water content of rats in a dose-dependent manner. More interestingly, AQP3 expression was suppressed by RFP treatment both in the rat colons and in HT-29 cells, while the NF-B pathway-mediated PGE 2 production was activated. Interestingly, pretreating rats with BAY-11-7082 (NF-B inhibitor) or indomethacin (COX-2 inhibitor) and RFP neither induced diarrhea nor decreased the AQP3 expression in the colon. Conclusions. The purgative property of the purified resin glycoside fraction was attributed to NF-B activation in the colon, which increased the COX-2-mediated secretion of PGE 2 . PGE 2 decreased AQP3 expression which inhibits water absorbed from the intestine to the blood vessel side, resulting in the laxative effect of RFP.