ReferenceID 1591

Costunolide ameliorates intestinal dysfunction and depressive behaviour in mice with stress-induced irritable bowel syndrome via colonic mast cell activation and central 5-hydroxytryptamine metabolism

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Irritable bowel syndrome (IBS) is a common chronic functional bowel disease, associated with a high risk of depression and anxiety. The brain-gut axis plays an important role in the pathophysiological changes involved in

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Reference Id
1591
Evidence Id
18181
Core Evidence Id
18181
Source Reference Id
3192
Herb2 Reference Id
HBREF003989
Subject Paper Key
HBIN021599_33977961
Pubmed Id
33977961
Doi
10.1039/d0fo03340e
Paper Title
Costunolide ameliorates intestinal dysfunction and depressive behaviour in mice with stress-induced irritable bowel syndrome via colonic mast cell activation and central 5-hydroxytryptamine metabolism
Paper Abstract
Irritable bowel syndrome (IBS) is a common chronic functional bowel disease, associated with a high risk of depression and anxiety. The brain-gut axis plays an important role in the pathophysiological changes involved in IBS; however, an effective treatment for the same is lacking. The natural compound costunolide (COS) has been shown to exert gastroprotective, enteroprotective, and neuroprotective effects, but its therapeutic effects in IBS are unclear. Our study explored the effect of COS on intestinal dysfunction and depressive behaviour in stress-induced IBS mice. Mice were subjected to chronic unpredictable mild stress to trigger IBS, and some were administered COS. Behavioural tests, histochemical assays, western blotting, and measurement of 5-hydroxytryptamine (5-HT) levels in the colon and hippocampus were applied to monitor the physiological and molecular consequences of COS treatment in IBS mice. COS administration relieved intestinal dysfunction and depression-like behaviours in IBS mice. Improvements in low-grade colon inflammation and intestinal mucosal permeability, inhibition of the activation of mast cells, upregulation of colonic Occludin expression, and downregulation of Claudin 2 expression were also observed. COS was also found to upregulate GluN2A, BDNF, p-ERK1/2, and p-CREB expression and 5-HT levels in hippocampal cells but inhibited 5-HT metabolism. Molecular docking showed that COS could form hydrogen bonds with the serotonin transporter (SERT) to affect the reuptake of 5-HT in the intercellular space. In conclusion, COS alleviates intestinal dysfunction and depressive behaviour in stress-induced IBS mice by inhibiting mast cell activation in the colon and regulating 5-HT metabolism in the central nervous system.
Journal
Food Funct
Publish Year
2021
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Anxiety; Intestinal Dysfunction; Low-grade Colon Inflammation; Depression; Irritable Bowel Syndrome; Chronic Functional Bowel Disease
Paper Title Cn
Paper Title En
Costunolide ameliorates intestinal dysfunction and depressive behaviour in mice with stress-induced irritable bowel syndrome via colonic mast cell activation and central 5-hydroxytryptamine metabolism
Bilingual Status
semi_complete