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Open AccessArticle

Grape Seed Extract Eliminates Visceral Allodynia and Colonic Hyperpermeability Induced by Repeated Water Avoidance Stress in Rats

1
Institute for Health Care Science, Suntory Wellness Limited, Seikadai 8-1-1, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan
2
Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan
3
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this manuscript.
Nutrients 2019, 11(11), 2646; https://doi.org/10.3390/nu11112646
Received: 9 September 2019 / Revised: 17 October 2019 / Accepted: 28 October 2019 / Published: 4 November 2019
(This article belongs to the Special Issue Polyphenol-Rich Foods for Human Health and Disease)
Grape seed extract (GSE) is rich in polyphenols composed mainly of proanthocyanidins, which are known to attenuate proinflammatory cytokine production. Repeated water avoidance stress (WAS) induces visceral allodynia and colonic hyperpermeability via toll-like receptor 4 (TLR4) and proinflammatory cytokine pathways, which is a rat irritable bowel syndrome (IBS) model. Thus, we explored the effects of GSE on repeated WAS (1 h for 3 days)-induced visceral allodynia and colonic hyperpermeability in Sprague-Dawley rats. Paracellular permeability, as evaluated by transepithelial electrical resistance and flux of carboxyfluorescein, was analyzed in Caco-2 cell monolayers treated with interleukin-6 (IL-6) and IL-1β. WAS caused visceral allodynia and colonic hyperpermeability, and intragastric administration of GSE (100 mg/kg, once daily for 11 days) inhibited these changes. Furthermore, GSE also suppressed the elevated colonic levels of IL-6, TLR4, and claudin-2 caused by WAS. Paracellular permeability was increased in Caco-2 cell monolayers in the presence of IL-6 and IL-1β, which was inhibited by GSE. Additionally, GSE suppressed the claudin-2 expression elevated by cytokine stimulation. The effects of GSE on visceral changes appear to be evoked by suppressing colonic TLR4-cytokine signaling and maintaining tight junction integrity. GSE may be useful for treating IBS. View Full-Text
Keywords: grape seed extract; visceral hypersensitivity; gut permeability; gut barrier; tight junction; inflammation; toll-like receptor 4 grape seed extract; visceral hypersensitivity; gut permeability; gut barrier; tight junction; inflammation; toll-like receptor 4
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MDPI and ACS Style

Arie, H.; Nozu, T.; Miyagishi, S.; Ida, M.; Izumo, T.; Shibata, H. Grape Seed Extract Eliminates Visceral Allodynia and Colonic Hyperpermeability Induced by Repeated Water Avoidance Stress in Rats. Nutrients 2019, 11, 2646.

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