Paeoniflorin Improved Constipation in the Loperamide-Induced Rat Model via TGR5/TRPA1 Signaling-Mediated 5-Hydroxytryptamine Secretion
Yu Zhan 1 2, Yong Wen 3 4, Liang-Liang Zhang 3, Xu-Long Shen 5, Xiao-Hui Chen 2, Xiao-Hai Wu 6, Xue-Gui Tang 7 8
Slow transit constipation (STC) is a very common kind of constipation having a high incidence rate and a lot of patients. We aimed to research the therapeutic effects and potential mechanism of paeoniflorin (PAE) on loperamide-caused Sprague Dawley (SD) rat constipation models. Rats with loperamide-caused constipation were orally administered different concentrations of PAE (10, 20, or 40 mg/kg). In vitro, enterochromaffin (EC)-like RIN-14B cells were given 20, 40, or 80 |¨¬g/ml PAE. We discovered that PAE treatment considerably improved the signs and symptoms of constipation and elevated the intestinal transit rate. Hematoxylin and eosin (H&E) staining demonstrated that PAE alleviated colonic tissue pathological damage. Besides, our results implied that PAE concentration-dependently promoted the information of 5-hydroxytryptamine (5-HT) catalyzed by tryptophan hydroxylase (Tph)-one in the serum of loperamide-caused rats as well as in RIN-14B cells. Western blot and immunofluorescence (IF) stain established that PAE also promoted the expression of G protein-coupled BA receptor 1 (TGR5), transient receptor potential ankyrin 1 (TRPA1), phospholipase C (PLC)-|?1, and phosphatidylinositol 4,5-bisphosphate (PIP2) in vivo as well as in vitro. RIN-14B cells were cotreated having a TGR5 inhibitor (SBI-115) look around the mechanism of PAE in controlling the five-HT secretion. We observed inhibition of TGR5 reversed the rise of 5-HT secretion caused by PAE in RIN-14B cells. We provided evidence that PAE could promote 5-HT release from EC cells and improve constipation by activating the TRPA1 funnel and PLC-|?1/PIP2 signaling. Thus, PAE may provide therapeutic effects for patients with STC.