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

Kobayashi, Yutaro, Kovacs-Nolan, Jennifer, Matsui, Toshiro, Minie, Yoshinori
Journal of agricultural and food chemistry 2015 v.63 no.26 pp. 6041-6050
IKappaB kinase, agonists, anti-inflammatory activity, body weight, calcium, calcium channels, colitis, colon, dextran, inflammation, interleukins, mice, mitogen-activated protein kinase, myocytes, secretion, smooth muscle, sodium sulfate, tumor necrosis factors
Trp-His, the anti-atherosclerotic dipeptide, exerted an antiproliferative effect on vascular smooth muscle cells by L-type Ca2+ channel blocker-like effect. The beneficial potential by the blockade of Ca2+ 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 Ca2+ channel blockers, was impaired by the presence of Ca2+ 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 Ca2+ channels.