Maren Pills Improve Constipation via Regulating AQP3 and NF-κB Signaling Pathway in Slow Transit Constipation In Vitro and In Vivo

Abstract

Background. Maren pills have been used to treat constipation. Aquaporin 3 (AQP3) plays a vital role in regulating water transfer in the colon. It has been reported that the downregulation of AQP3 can regulate liquid water metabolism and intestinal permeability in irritable bowel syndrome (IBS) rats’ colon via NF-κB pathway. In this study, we investigated whether the laxative effect of Maren pills is associated with the regulation of AQP3 and NF-κB signaling pathway in the colon. Methods. The compound diphenoxylate suspension-induced STC rats received Maren pills intragastrically for 1 consecutive week to evaluate the laxative effect of Maren pills involving the regulation of AQP3 and NF-κB signaling pathway. Moreover, human intestinal epithelial cells (HT-29) were treated with drug serum to obtain in vitro data. Results. Our results revealed that treatment with Maren pills increased the stool number, moisture content of feces, and intestinal transit rate in a dose-dependent manner. Maren pills significantly increased the AQP3, fibrosis transmembrane conductance regulator (CFTR), and protein kinase A (PKA) proteins in the colon of rats and in HT-29 cells. Mechanistically, Maren pills obviously inhibited the activation of NF-κB pathway in the colon of rats and in HT-29 cells. Conclusion. These results suggest that the laxative effect of Maren pills is associated with the increased expression of AQP3 by downregulating NF-κB signal pathway.

Novel Characterization of Constipation Phenotypes in ICR Mice Orally Administrated with Polystyrene Microplastics

“…Furthermore, we investigated whether the increase of water intake during MP-induced defecation delay is associated with the regulation of membrane water balance in the mid colon. Since AQP3 regulates the liquid water metabolic abnormalities and intestine permeability alteration via MAPK/NF-κB pathway, alterations in the AQP3 and AQP8 transcriptions and MAPK/NF-κB signaling pathway were examined in the mid colon of subset groups [ 22 , 23 ]. The mRNA levels of AQP3 and AQP8 were remarkably decreased in the LoMP, MiMP, and HiMP treated groups, as compared to the Vehicle treated group ( Figure 10 a).…”

The potential of Quercetin to protect against loperamide‐induced constipation in rats

“…AQPs can affect the changes in colonic water metabolism and intestinal permeability (Deng et al., 2018; Zhan et al., 2020). Water is transported from the luminal side to the vascular side through AQP3 because the osmotic pressure is lower in the colonic lumen than in the blood vessel, and the feces are concentrated.…”

“…Gastrointestinal hormone VIP plays an important role in water transport in the intestine (Yi et al., 2019). VIP, one of the most abundant neuropeptides in the intestine, has been shown to play an important role in water transport by regulating the cAMP‐PKA‐AQP signal transduction pathway (Gan, Ai, et al., 2020; Gan, Liang, et al., 2020; Zhan et al., 2020). In this study, we found that QCT can downregulate the expressions of AQP3 mRNA and protein via VIP‐cAMP‐PKA‐AQP3 signaling pathway, which prevent the reabsorption of water in the lumen by blood vessels, thus improving constipation.…”

Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway

“…36 Abnormal expression of AQP3 leads to excessive intestinal water in the cells or intestinal mucus secretion, leading to constipation. 37 VIP regulates intestinal motility and intestinal water metabolism, which is closely related to constipation. [38][39][40] VIP regulates intestinal water metabolism by affecting AQP3 expression in intestinal epithelial cells.…”