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. 2024 Jun 18;25(12):6694.
doi: 10.3390/ijms25126694.

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

Lili Jiang  1 , Youling Hao  1 , Qianjun Li  2 , Zhaolai Dai  1
Affiliations

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

Lili Jiang et al. Int J Mol Sci. .

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 < 0.05) the short-circuit current, and 100 μM chlorogenic acid (CGA) (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 < 0.05) the mRNA levels of Tph1. In addition, 10 μM IAld or 100 μM ILA upregulated (p < 0.05) the expression of monoamine oxidase A (Maoa). However, 10 μM CGA or 100 μM PA downregulated (p < 0.05) Maoa expression. All selected phytochemicals and Trp metabolites upregulated (p < 0.05) the expression of Htr4 and Htr7 compared to that of the control group. VMA and CGA reduced (p < 0.05) the ratios of 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: Ussing chamber; ileum; indoles; phytochemicals; serotonin receptors.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Representative diagram comparing the short-circuit current (Isc) of the ileum of mice following the administration of phytochemicals.
Figure 2
Figure 2
Effects of different phytochemicals and Trp metabolites on the gene expression of 5-HT metabolism-related enzymes, including Tph1 (A) and Maoa (B) in the ileum of mice. The data in the charts are the means ± SEMs. * p < 0.05, ** p < 0.01, and *** p < 0.001 compared to the control group. Tph1, tryptophan hydroxylase 1; Maoa, monoamine oxidase A; VMA, vanillylmandelic acid; PA, perillic acid; MurA, muramic acid; CA, cinnamic acid; CGA, chlorogenic acid; NAS, N-acetylserotonin; ILA, indolelactic acid; IAld, indoleacetaldehyde. The number of animals is shown in Table 1.
Figure 3
Figure 3
Effects of different phytochemicals and Trp metabolites on the protein abundance of tryptophan hydroxylase 1 (Tph1) in the ileum of mice. The data in the charts are the means ± SEMs, n = 3. CA, cinnamic acid; PA, perillic acid; IAld, indoleacetaldehyde; NAS, N-acetylserotonin.
Figure 4
Figure 4
Effects of different phytochemicals and Trp metabolites on the expression of serotonin receptor genes, including Htr1a (A), Htr4 (B), and Htr7 (C) in the ileum of mice. The data in the charts are the means ± SEMs. * p < 0.05, ** p < 0.01, and *** p < 0.001 compared to the control group. The number of animals is shown in Table 1. VMA, vanillylmandelic acid; PA, perillic acid; MurA, muramic acid; CA, cinnamic acid; CGA, chlorogenic acid; NAS, N-acetylserotonin; ILA, indolelactic acid; IAld, indoleacetaldehyde.
Figure 5
Figure 5
Different phytochemicals, including PA and VMA (A), and CGA and Curcumin (B) on the serotonin receptor gene ratios in the ileum of mice. The data in the charts are the means ± SEMs. * p < 0.05, ** p < 0.01, and *** p < 0.001 compared to the control group. The number of animals is shown in Table 1. CGA, chlorogenic acid; PA, perillic acid; VMA, vanillylmandelic acid.
Figure 6
Figure 6
A photo of the Ussing chamber system used in this study.
See this image and copyright information in PMC

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