Dietary limonene promotes gastrointestinal barrier function via upregulating tight/adherens junction proteins through cannabinoid receptor type-1 antagonistic mechanism and alters cellular metabolism in intestinal epithelial cells

被引：1

作者：

Kumar, K. J. Senthil ^{[1
,2
]}

Vani, M. Gokila ^{[3
]}

Dakpa, Gyaltsen ^{[4
,5
]}

Wang, Sheng-Yang ^{[3
,4
,6
,7
]}

机构：

[1] Natl Chung Hsing Univ, Bachelor Program Biotechnol, Taichung, Taiwan

[2] Natl Chung Hsing Univ, Ctr Gen Educ, Taichung, Taiwan

[3] Natl Chung Hsing Univ, Dept Forestry, Taichung 402, Taiwan

[4] Acad Sinica, Mol & Biol Agr Sci Program, Taiwan Int Grad Program, Taipei, Taiwan

[5] Natl Chung Hsing Univ, Grad Inst Biotechnol, Taichung, Taiwan

[6] Acad Sinica, Agr Biotechnol Res Ctr, Taipei, Taiwan

[7] Natl Chung Hsing Univ, Acad Circle Econ, Special Crop & Metabolome Discipline Cluster, Taichung, Taiwan

来源：

BIOFACTORS | 2025年 / 51卷 / 01期

关键词：

adherence junction; CB1R; intestinal epithelial cells; limonene; metabolites; tight junction; MAMMALIAN-CELLS; EXPRESSION; INCREASE;

D O I：

10.1002/biof.2106

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Limonene, a dietary monocyclic monoterpene commonly found in citrus fruits and various aromatic plants, has garnered increasing interest as a gastrointestinal protectant. This study aimed to assess the effects of limonene on intestinal epithelial barrier function and investigate the involvement of cannabinoid receptor type-1 (CB1R) in vitro. Additionally, the study focused on examining the metabolomic changes induced by limonene in the intestinal epithelial cells (Caco-2). Initial analysis of transepithelial electrical resistance (TEER) revealed that both l-limonene and d-limonene, isomers of limonene, led to a dose- and time-dependent increase in TEER in normal cells and those inflamed by pro-inflammatory cytokines mixture (CytoMix). Furthermore, both types of limonene reduced CytoMix-induced paracellular permeability, as demonstrated by a decrease in Lucifer yellow flux. Moreover, d-limonene and l-limonene treatment increased the expression of tight junction molecules (TJs) such as occludin, claudin-1, and ZO-1, at both the transcriptional and translational levels. d-Limonene upregulates E-cadherin, a molecule involved in adherens junctions (AJs). Mechanistic investigations demonstrated that d-limonene and l-limonene treatment significantly inhibited CB1R at the protein, while the mRNA level remained unchanged. Notably, the inhibitory effect of d-limonene on CB1R was remarkably similar to that of pharmacological CB1R antagonists, such as rimonabant and ORG27569. d-limonene also alters Caco-2 cell metabolites. A substantial reduction in beta-glucose and 2-succinamate was detected, suggesting limonene may impact intestinal epithelial cells' glucose uptake and glutamate metabolism. These findings suggest that d-limonene's CB1R antagonistic property could effectively aid in the recovery of intestinal barrier damage, marking it a promising gastrointestinal protectant. d-Limonene treatment protects cytokine mixture-induced CB1R associated intestinal barrier function in Caco-2 cells. image

引用

页数：19