Xuanhuang Runtong Tablets Relieve Slow Transit Constipation in Mice by Regulating TLR5/IL‐17A Signaling Mediated by Gut Microbes

Abstract

This study aims to investigate the regulation effects of Xuanhuang Runtong tablets (XHRTs) on intestinal microbes and inflammatory signal toll receptor 5 (TLR5)/interleukin-17A (IL-17A) in STC mice. First, high-performance liquid chromatography (HPLC) was used to verify the composition of XHRT and quality control. Then, the defecation ability of STC mice was evaluated by measuring fecal water content and intestinal transit function. The pathological examination of colonic mucosa was observed by Alcian Blue and periodic acid Schiff (AB-PAS) staining. 16S ribosomal DNA (16S rDNA) genes were sequenced to detect the fecal microbiota. Western blotting, immunofluorescence, and real-time fluorescence quantitative PCR (qRT-PCR) were applied to detect the expression of aquaporin 3 (AQP3), connexin 43 (Cx43), TLR5, and IL-17A. The defecation function of the STC mice was significantly decreased. The amount of mucus secretion and the thickness of the colonic mucus layer were decreased, and the number of microbial species in the intestinal wall, such as Firmicutes/Bacteroidetes, anaerobic bacteria, and Alistipes, were also decreased. In addition, the expression of AQP3 and Cx43 was disordered, and the inflammatory factorsTLR5 and IL-17A were activated in the colon. The changes in the above indicators were significantly reversed by XHRT. This study demonstrates that XHRT provides a new strategy for the treatment of slow transit constipation by regulating the activation of the intestinal inflammatory signal TLR5/IL-17A mediated by gut microbes.

Qi Lang formula relieves constipation via targeting SCF/c-kit signaling pathway: An integrated study of network pharmacology and experimental validation

“…Decreased expression of CX43 might lead to weakened cell-to-cell communication, suggesting that the onset of constipation may be related to the destruction of the gap junction between cells. The expression of CX43 in the model group we studied was reduced, so it can be seen that CX43 as a channel changes, so that the electrophysiological signals of the colon cannot be produced, and also affect the signal transmission to the smooth muscle of the colon, which in turn leads to colonic motility disorders, which may be one of the important mechanisms causing constipation [ 39 ].…”

Roles and regulation of Aquaporin-3 in maintaining the gut health: an updated review

“…AQPs represent important targets for traditional Chinese medicine in the treatment of digestive disorder including constipation ( Huang et al, 2022 ). A recent study showed that Xuanhuang Runtong tablets could reverse the disorder of AQP3 expression and thus relieve slow transit constipation in mice ( Liang et al, 2023 ). Moreover, the laxative effect of Daiokanzoto has been confirmed when used as a long-term treatment for chronic constipation probably by maintaining a persistent decrease of AQP3 expression and gut microbiota homeostasis ( Kon et al, 2018b ).…”