Laxative action of sennoside A, which causes decreased colonic aquaporin‐3 expression, is controlled by the anti‐inflammatory effect of glycyrrhizin.

ABSTRACT: Aim: The laxative action of daiokanzoto (a compound containing rhubarb and glycyrrhiza) is thought to be due to sennoside A, an ingredient in rhubarb. Glycyrrhizin, which has anti‐inflammatory effects, is the main ingredient in glycyrrhiza, and it alleviates adverse reactions, such as abdominal pain and painful defecation, due to rhubarb. No consensus has been reached, however, on why daiokanzoto contains glycyrrhiza. We found that sennoside A exerts a laxative action by decreasing aquaporin‐3 (AQP3) expression through the activation of macrophages in the colon. This study analyzed the effect of glycyrrhizin on the laxative action of sennoside A focusing on AQP3 expression. Methods: Sennoside A, glycyrrhizin, or a combination of both were given orally to rats, and diarrhea severity was assessed. The expression of AQP3, inflammatory cytokines, and cyclo‐oxygenase (COX) was analyzed. Results: Although diarrhea occurred when sennoside A and glycyrrhizin were given together orally, it was less severe than when sennoside A was used alone, and, correspondingly, only sennoside A inhibited AQP3 expression to a greater extent than the combination of both drugs. When glycyrrhizin was given concomitantly, the sennoside A‐induced increased expression of pro‐inflammatory cytokines and COX‐2 was suppressed. Conclusions: The laxative action of sennoside A and the decreased expression of AQP3 were suppressed when sennoside A and glycyrrhizin were given concomitantly, likely due to the anti‐inflammatory effects of glycyrrhizin. This indicates that glycyrrhizin both attenuates the adverse reactions caused by sennoside A and plays a role in its laxative action. [ABSTRACT FROM AUTHOR]