Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin-3 expression in the colon

Risako Kon,Moe Minami,Kiyoshi Sugiyama,Saki Kato,Yukari Matsunaga,Hiroshi Kimura,Miho Yamamura,Nobutomo Ikarashi

doi:10.1007/s11418-018-1174-1

Abstract

Daiokanzoto (DKT) exerts its laxative effect via colonic inflammation caused by sennoside A in Daio (rhubarb). Previously, we showed that the laxative effect of sennoside A is related to decreased aquaporin-3 (AQP3) expression in mucosal epithelial cells due to colonic inflammation. We also found that a combination of glycyrrhizin, an ingredient in Kanzo (glycyrrhiza), and sennoside A attenuates the inflammatory response induced by sennoside A and reduces its laxative effect. These findings indicate that DKT may be a long-term treatment for chronic constipation, but there is no evidence supporting this hypothesis. In this study, we analyzed the laxative effect of repeated DKT administration, focusing on AQP3 expression in the colon. After rats were treated for 7 days, decreased AQP3 expression and the onset of diarrhea were observed in the DKT group, but were not seen in the Daio group either. Although the relative abundance of gut microbiota after repeated DKT administration was similar to that after control treatment, Daio reduced Lactobacillaceae, Bifidobacteriaceae, and Bacteroidaceae levels and markedly increased Lachnospiraceae levels. In this study, we show that DKT has a sustained laxative effect, even upon repeated use, probably because it maintains decreased AQP3 expression and gut microbiota homeostasis. This outcome therefore indicates that DKT can be used as a long-term treatment for chronic constipation.

Highlights

Daiokanzoto (DKT) is a Kampo medicine composed of two crude drugs, Daio and Kanzo, that can be repeatedly used for a long period to relieve constipation or related symptoms
We investigated the laxative effects of repeated administration of DKT and of Daio to establish scientific evidence for DKT as a therapeutic for chronic constipation and clarified the role of Kanzo in DKT
In rats given a single dose of DKT, fecal water content was significantly increased compared to that in the control group, and AQP3 expression in colonic mucosal epithelial cells was decreased

Summary

Introduction

Daiokanzoto (DKT) is a Kampo medicine composed of two crude drugs, Daio (rhubarb) and Kanzo (glycyrrhiza), that can be repeatedly used for a long period to relieve constipation or related symptoms. We found that pretreatment of rats with indomethacin, an anti-inflammatory drug, suppressed the sennoside A-induced decrease in AQP3 expression, which weakened the laxative effect of sennoside A [2]. Kanzo, another component of DKT, contains glycyrrhizin and has an anti-inflammatory effect. It has been reported that the longterm use of these drugs causes adverse reactions, including cathartic colon and melanosis coli, which may progress to intestinal pseudo-obstruction or colon cancer [4,5,6] Stimulant laxatives such as Daio and senna are unsuitable for long-term use. We analyzed the mechanism responsible for the change in AQP3 expression upon repeated administration of DKT

Materials and methods

Result

Discussion

Findings

Compliance with ethical standards