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.

The potential of food protein‐derived anti‐inflammatory peptides against various chronic inflammatory diseases

“…Given the concerns about the side effects, there has been also a substantial increase in public and scientific awareness about natural compounds and their derivatives as safer alternatives for the treatment and management of chronic diseases. A substantial amount of scientific evidence has suggested that food‐derived compounds, both nutrients and non‐nutrients, can modulate chronic inflammatory conditions . Food‐derived compounds are not organ‐ or tissue‐specific and may modulate both pro‐inflammatory and/or anti‐inflammatory cytokines.…”

The Potential of Food Protein-Derived Bioactive Peptides against Chronic Intestinal Inflammation

“…There are four possible mechanism pathways for BAPs to attenuate chronic intestinal inflammation: NF- κ B, MAPK, Janus kinase-signal transducer and activator of transcription (JAK-STAT), and peptide transporter 1 (PepT1) ( Figure 2 ) [ 2 , 7 , 10 , 20 , 37 – 41 ]. Through inhibiting these pathways, BAPs can act the anti-inflammatory function in intestinal cells.…”

“…After being stimulated, JNK accumulates in the nucleus and causes the corresponding gene (IL-1 and TNF- α ) expression, resulting in inflammatory response ( Figure 2 ) [ 44 ]. Various food protein-derived BAPs can inhibit inflammation via this MAPK pathway, such as DEDTQAMPFR, DEDTQAMPF [ 18 ], FLV [ 20 ], MLGATSL, MSYSAGF [ 18 ], β -Ala-His [ 35 ], pyroGlu-Leu [ 36 ], DIKTNKPVIF [ 45 ], VPP [ 46 ], WH [ 41 ], γ -EC, and γ -EV [ 47 ].…”

“…Numbers of BAPs derived from various food proteins (milk, plant, egg, soybean, meat, wheat, rice, potato, corn silk, fish, etc.) have been found to be well suited to treat inflammation or IBD symptoms in vivo ( Table 2 ), such as Ala-Gln (AQ) [ 9 , 52 – 54 ], DIKTNKPVIF [ 45 ], EWP [ 55 ], GLTSK [ 56 ], glycomacropeptide [ 57 – 60 ], lunasin [ 15 ], IRW [ 11 , 61 – 63 ], IQW [ 62 – 64 ], KGHYAERVG [ 65 ], KPV [ 66 ], PTGADY [ 67 ], QCQCAVEGGL [ 68 ], QEPVL, QEPV [ 6 ], RILSILRHQNLLKELQDLAL [ 69 ], SSEDIKE [ 70 ], TMKLLLVTL [ 43 ], VPP [ 31 , 46 , 71 , 72 ], IPP [ 71 , 72 ], VPY [ 33 ], WH [ 41 ], casein hydrolysates [ 73 ], soybean dipeptides and tripeptides [ 74 ], peptide P-317 [ 75 ], pyroGlu-Leu [ 76 ], β -Casofensin [ 77 ], γ -EC, and γ -EV [ 47 ]. These studies suggest that oral administration of food-derived BAPs have anti-inflammatory effects, and they can be the therapeutic agents for inflammatory-related diseases, including IBD [ 78 ].…”

Effects of Lysine deficiency and Lys-Lys dipeptide on cellular apoptosis and amino acids metabolism

“…In mammals, uptake of small peptides by the oligo/dipeptide transporters (pept1) provides an effective and energy‐saving intracellular source of AA . Recently, several dipeptides have been identified to exert various physiological functions, such as antiatherosclerotic effects (Trp‐His) , antioxidant function (Ala‐Gln and Asn‐Trp) , and anti‐inflammatory (Gln‐Cys and Gln‐Val) . Thus, dipeptides containing Lys are expected to exert positive effects in the application fields of which free Lys or its salts show lower bioavailability.…”