Study on the therapeutic effects of the primary active ingredients in cinnamon oil for constipation-predominant irritable bowel syndrome and their regulatory effects on the 5-HT signaling pathway and gut microbiota.

Cinnamon oil exhibits therapeutic potential against constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to evaluate the efficacy and mechanisms of its main components-cinnamaldehyde (CAL), cinnamyl alcohol (COL), and trans-cinnamic acid (TCA)-in IBS-C. This study established an IBS-C mouse model using loperamide hydrochloride and restraint stress, and evaluated indicators such as body weight, the number of fecal pellets, fecal water content, visceral hypersensitivity, and small intestinal propulsion rate. The analysis was performed via HE staining, ELISA, Western blot, qRT-PCR, and 16S rRNA sequencing. All three components ameliorated low-grade immune cell infiltration in colonic tissue and reduced serum levels of IL-6, IL-8, and TNF-α. They also increased motilin (MTL) and acetylcholine (Ach) levels; all except trans-cinnamic acid low-dose (TCA-L) increased gastrin (Gas) levels, and all except TCA-L and trans-cinnamic acid high-dose (TCA-H) increased 5-HT levels. Cinnamaldehyde high-dose (CAL-H), cinnamyl alcohol high-dose (COL-H), and TCA-H upregulated the expression of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and 5-hydroxytryptamine receptor 4 (5-HT4R) and partially modulated gut microbiota composition. CAL showed favorable effects under the present experimental conditions. The three components alleviated IBS-C symptoms partially through modulating the 5-HT signaling pathway and gut microbiota, with CAL showing the most pronounced effects under the present experimental conditions.