Cinnamic Acid, Perillic Acid, and Tryptophan Metabolites Differentially Regulate Ion Transport and Serotonin Metabolism and Signaling in the Mouse Ileum In Vitro

Abstract

Phytochemicals and tryptophan (Trp) metabolites have been found to modulate gut function and health. However, whether these metabolites modulate gut ion transport and serotonin (5-HT) metabolism and signaling requires further investigation. The aim of this study was to investigate the effects of selected phytochemicals and Trp metabolites on the ion transport and 5-HT metabolism and signaling in the ileum of mice in vitro using the Ussing chamber technique. During the in vitro incubation, vanillylmandelic acid (VMA) reduced (p p = 0.12) and perillic acid (PA) (p = 0.14) had a tendency to reduce the short-circuit current of the ileum. Compared with the control, PA and N-acetylserotonin treatment upregulated the expression of tryptophan hydroxylase 1 (Tph1), while 100 μM cinnamic acid, indolelactic acid (ILA), and 10 μM CGA or indoleacetaldehyde (IAld) treatments downregulated (p Tph1. In addition, 10 μM IAld or 100 μM ILA upregulated (p Maoa). However, 10 μM CGA or 100 μM PA downregulated (p Maoa expression. All selected phytochemicals and Trp metabolites upregulated (p Htr4 and Htr7 compared to that of the control group. VMA and CGA reduced (p Htr1a/Htr7 and Htr4/Htr7. These findings may help to elucidate the effects of phytochemicals and Trp metabolites on the regulation of gut ion transport and 5-HT signaling-related gut homeostasis in health and disease.

Keywords

• phytochemicals
• indoles
• serotonin receptors
• Ussing chamber
• ileum