Combination of fenchone and sodium hyaluronate ameliorated constipation‐predominant irritable bowel syndrome and underlying mechanisms

Abstract We sought to explore the protective effect of the combination of fenchone (FE) and sodium hyaluronate (SH) on ice water‐induced IBS‐C rats and the potential mechanism. The neurotransmitter levels, including substance P (SP), motilin (MTL), 5‐hydroxytryptamine (5‐HT), and vasoactive intestinal peptide (VIP), were determined by ELISA methods. The stem cell factors (SCF)/c‐Kit signaling pathway‐related protein and mRNA levels were determined by western blot and reverse transcription quantitative polymerase chain reaction (RT‐qPCR) analyses, respectively. The expressions of tight ZO‐1, Occludin, and Claudin‐1 were also measured by western blot assay and immunofluorescence staining. The 16S rRNA gene sequence was used to measure the composition of gut microbiota. The co‐administration of FE and SH improved the body weight, number of fecal pellets, fecal moisture, abdominal with drawal reflex score, and gastrointestinal transit rate in IBS‐C rats. The unique efficacy of combination depended on the regulation of balance between excitatory and inhibitory neurotransmitters, enhancement of intestinal barrier function, and activation of SCF/c‐Kit pathway. The gut microbiota structure was also restored. The ability of FE combined with SH to regulate SCF/c‐Kit signaling pathway, enhance intestinal barrier function, and modulate gut microbiota contributes to their efficacy in managing IBS‐C in rats.