Paeoniflorin alleviates constipation in CKD mice by regulating tryptophan metabolism

QIU Jun; NIE Huibin; YAO Fenghua; HAN Bo; ZHAN Yu

doi:10.13506/j.cnki.jpr.2025.04.003

Abstract：Objective To investigate the effect of paeoniflorin(PF)on improving constipation symptoms in adenine-in-duced chronic kidney disease(CKD)mice.Methods Thirty C57BL/6 mice were randomly assigned to five groups:control,model,linaclotide,and low-and high-dose paeoniflorin groups,with six mice in each group.To induce the CKD model,mice in all groups except the control were fed a 0.2％adenine diet for six weeks.The low-and high-dose paeoniflorin groups were ad-ministered 100 and 200 mg·(kg·d)-1 of paeoniflorin via gavage,respectively,while the linaclotide group received 100 µg·(kg·d)-1 of linaclotide suspension via gavage,serving as a positive control for constipation treatment.The control and model groups were given an equivalent volume of distilled water for 14 days.Fecal water content,intestinal transit time,and in-testinal motility were measured to assess the severity of constipation.The expression of key proteins involved in tryptophan me-tabolism(TPH1,AHR,and IDO1)were quantified by Western blotting.Intestinal contents of mice were collected for intestinal flora sequencing to explore the effect of paeoniflorin on intestinal flora.Results Compared to the control group,the model group showed significantly elevated serum creatinine and blood urea nitrogen levels,decreased fecal water content,prolonged intestinal transit time,reduced motility,and downregulated colonic TPH1,and AHR protein expression(P＜0.05).Compared with the model group,the paeoniflorin-treated mice exhibited decreased serum creatinine and blood urea nitrogen levels,in-creased fecal water content and intestinal motility,shortened transit time,and upregulated colonic TPH1,and AHR protein ex-pression(P＜0.05).Furthermore,gut microbiome sequencing data indicated that paeoniflorin significantly modulated the compo-sition of fecal microbiota in adenine-induced CKD mice.Conclusion Paeoniflorin significantly alleviates constipation symp-toms in adenine-induced CKD mice,possibly through the regulation of intestinal tryptophan metabolism.