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The Anti-atherosclerotic Dipeptide, Trp-His, Reduces Intestinal Inflammation through the Blockade of L-Type Ca2+ Channels.

Abstract
Trp-His, the anti-atherosclerotic dipeptide, exerted an antiproliferative effect on vascular smooth muscle cells by L-type Ca(2+) channel blocker-like effect. The beneficial potential by the blockade of Ca(2+) channels on chronic intestinal inflammation, including inflammatory bowel disease (IBD), is unclear. Trp-His (100 or 250 mg/kg body weight/day) was administered for 14 days to BALB/c mice, and 5% dextran sodium sulfate (DSS) was administered to induce colitis in the last 7 days. Trp-His reduced DSS-induced typical colitis symptoms and cytokine expression in the colon. Trp-His inhibited interleukin (IL)-8 secretion in tumor necrosis factor (TNF)-α-stimulated HT-29 cells. The inhibitory effect of Trp-His, as well as that of Ca(2+) channel blockers, was impaired by the presence of Ca(2+) channel agonist Bay K 8644. The TNF-α-induced activation of mitogen-activated protein kinases (MAPKs) and IκBα were decreased by Trp-His. These results indicated that the anti-inflammatory effect of Trp-His may be involved in the blockade of L-type Ca(2+) channels.
AuthorsYutaro Kobayashi, Jennifer Kovacs-Nolan, Toshiro Matsui, Yoshinori Mine
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 63 Issue 26 Pg. 6041-50 (Jul 08 2015) ISSN: 1520-5118 [Electronic] United States
PMID26079480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Calcium Channels, L-Type
  • Dipeptides
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • tryptophyl-histidine
Topics
  • Animals
  • Anti-Inflammatory Agents (administration & dosage)
  • Calcium Channels, L-Type (genetics, immunology)
  • Dipeptides (administration & dosage)
  • Female
  • Humans
  • Inflammatory Bowel Diseases (drug therapy, genetics, immunology)
  • Interleukin-8 (genetics, immunology)
  • Intestines (drug effects, immunology)
  • Mice
  • Mice, Inbred BALB C
  • Tumor Necrosis Factor-alpha (genetics, immunology)

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