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Structure-Dependent Effects of Cinnamaldehyde Derivatives on TRPA1-Induced Serotonin Release in Human Intestinal Cell Models

  • Lieder, Barbara1
  • Hoi, Julia1
  • Burian, Nathalie1
  • Hans, Joachim2
  • Holik, Ann-Katrin1
  • Beltran Marquez, Leopoldo Raul1
  • Ley, Jakob P.2
  • Hatt, Hanns3
  • Somoza, Veronika2
  • 1 University of Vienna, Austria , (Austria)
  • 2 Symrise AG, Germany , (Germany)
  • 3 Ruhr-University Bochum, Germany , (Germany)
Published Article
Journal of Agricultural and Food Chemistry
American Chemical Society
Publication Date
Mar 12, 2020
DOI: 10.1021/acs.jafc.9b08163
PMID: 32162915
PMCID: PMC7205389
PubMed Central


Activation of the transient receptor potential (TRP) channel TRPA1 by cinnamaldehyde has been shown to stimulate serotonin release in enterochromaffin QGP-1 cells. However, the impact of cinnamaldehyde on serotonin release in enterocytes is less well understood. In addition, since the neurotransmitter serotonin plays a regulatory role in a large variety of gastrointestinal and metabolic functions, it is of interest to study which structural characteristics determine cinnamaldehyde-induced serotonin release by enterocytes. Thus, the present study analyzed serotonin release in differentiated Caco-2 cells as a model for enterocytes in comparison to enterochromaffin QGP-1 cells after stimulation with cinnamaldehyde and 17 naturally occurring structurally related compounds by means of a serotonin ELISA. Stimulation with cinnamaldehyde induced a dose-dependent increase in serotonin release starting from 0.5 mM in both cell lines, with a larger effect size in Caco-2 enterocytes compared to that in QGP-1 enterochromaffin cells. Serotonin release in Caco-2 cells induced by additional 17 structurally related compounds correlated with serotonin release in QGP-1 cells, showing the highest effects for coniferylaldehyde with a 15.84 ± 3.23-fold increase in Caco-2 cells, followed by the parent compound cinnamaldehyde (13.45 ± 2.15), cinnamyl alcohol (6.68 ± 1.08), and α-methyl-cinnamaldehyde (6.59 ± 0.93). Analysis of structural and molecular characteristics that modulate serotonin release in Caco-2 enterocytes revealed that the ability of a compound to activate TRPA1, demonstrated by means of HEK293 cells transiently expressing hTRPA1, is a decisive factor to stimulate serotonin release in Caco-2 enterocytes, preferring small, electrophilic compounds with a lower polar surface area. In addition, blocking of TRPA1 using 30 μM AP-18 significantly reduced the cinnamaldehyde-induced serotonin release by 30.0 ± 5.24%, confirming a TRPA1-dependent component in serotonin release by Caco-2 cells.

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