Zengye decoction regulated the expression of aquaporin in colon tissue of rats with constipation through miR-10a-5p targeting Drd2/AC/cAMP axis.

Abstract

Slow transit constipation (STC) is a colonic motor disorder characterized by a marked delay in the movement of substances through the colon. Traditional Chinese medicine (TCM) is a treasure trove of natural compounds, which is effective in treating constipation with relatively minor side effects. Zengye decoction (ZYD), a classic herbal formula in TCM, is used for moistening the intestines and relieving constipation. However, the molecular mechanism of ZYD in the treatment of constipation remains unclear. The present study aimed to investigate the effect and molecular mechanism of ZYD on STC. A loperamide-induced rat model and IEC-18 cells were used in vitro and in vivo. We found that ZYD increased the intestinal transit rate and fecal water content of STC rats in a dose-dependent manner. Furthermore, ZYD dose-dependently decreased the expression of Aquaporin (AQP)3 and increased AQP9 expression in the colon tissue of STC rats. Mechanistically, ZYD reduced the level of miR-10a-5p, increased the expression of dopamine receptor D2 (Drd2), and inhibited the activity of adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) signaling in the colon tissue of STC rats. However, miR-10a-5p overexpression reversed the improvement effect of ZYD on constipation. Moreover, miR-10a-5p targeted Drd2 and enhanced AC/cAMP signaling activation in IEC-18 cells. Also, miR-10a-5p regulated AQP3 and AQP9 expression in IEC-18 cells. Thus, ZYD alleviated constipation and aquaporin expression in STC rats, and its mechanism may be mediated by downregulating miR-10a-5p levels and inhibiting the Drd2/AC/cAMP axis. ZYD may be an efficient therapeutic strategy for constipation.