Downregulation of Aquaporin 3 Mediated the Laxative Effect in the Rat Colon by a Purified Resin Glycoside Fraction from Pharbitis Semen

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.After orally administering a purified resin glycoside fraction from Pharbitis Semen (RFP) to rats, the content of fecal water, AQP3, NF-κB, COX-2 expression, and the prostaglandin E2 (PGE2) 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 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-κB pathway-mediated PGE2 production was activated. Interestingly, pretreating rats with BAY-11-7082 (NF-κB inhibitor) or indomethacin (COX-2 inhibitor) and RFP neither induced diarrhea nor decreased the AQP3 expression in the colon.The purgative property of the purified resin glycoside fraction was attributed to NF-κB activation in the colon, which increased the COX-2-mediated secretion of PGE2. PGE2 decreased AQP3 expression which inhibits water absorbed from the intestine to the blood vessel side, resulting in the laxative effect of RFP.