The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation

Kovacs-Nolan, Jennifer; Zhang, Hua; Ibuki, Masahisa; Nakamori, Toshihiro; Yoshiura, Kenta; Turner, Patricia V.; Matsui, Toshiro; Mine, Yoshinori

doi:10.1016/j.bbagen.2012.07.007

Cited by 153 publications

(131 citation statements)

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“…Son et al (2008) identified the inhibitory effects of the peptide carnosine (β-Ala-His), which is derived from meat products, on modulating inflammatory responses in Caco-2 cells mediated by hPepT1 transportation. Kovacs-Nolan et al (2012) demonstrated that the soy protein-derived tripeptide VPY can be transported into Caco-2 cells by h-Pept1 and has anti-inflammatory activity to decrease pro-inflammatory mediator expression in vitro and in vivo in mice. Therefore, hPepT1 might be an alternative mechanism by which short-chain dietary peptides exert their anti-inflammatory activity to attenuate the inflammatory responses in colonic epithelial cells.…”

Section: Reduction Of Inflammation By Dietary Peptides Mediated By Prmentioning

confidence: 98%

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Bioactive dietary peptides and amino acids in inflammatory bowel disease

Zhang

Kovacs-Nolan

et al. 2014

Amino Acids

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Inflammatory bowel disease (IBD), most commonly ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammation of the gastrointestinal tract. Patients affected with IBD experience symptoms including abdominal pain, persistent diarrhea, rectal bleeding, and weight loss. There is no cure for IBD; thus treatments typically focus on preventing complications, inducing and maintaining remission, and improving quality of life. During IBD, dysregulation of the intestinal immune system leads to increased production of pro-inflammatory cytokines, such as TNF-α and IL-6, and recruitment of activated immune cells to the intestine, causing tissue damage and perpetuating the inflammatory response. Recent biological therapies targeting specific inflammatory cytokines or pathways, in particular TNF-α, have shown promise, but not all patients respond to treatment, and some individuals become intolerant to treatment over time. Dietary peptides and amino acids (AAs) have been shown to modulate intestinal immune functions and influence inflammatory responses, and may be useful as alternative or ancillary treatments in IBD. This review focuses on dietary interventions for IBD treatment, in particular the role of dietary peptides and AAs in reducing inflammation, oxidative stress, and apoptosis in the gut, as well as recent advances in the cellular mechanisms responsible for their anti-inflammatory activity.

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Section: Reduction Of Inflammation By Dietary Peptides Mediated By Prmentioning

confidence: 98%

“…Dietary AA-and peptide-based interventions have been shown to have therapeutic efficacy to attenuate intestinal inflammation (Kovacs-Nolan et al 2012). Those interventions have a limited toxic effect compared with the pharmaceutical approaches used to treat IBD patients.…”

Section: Novel Cellular Mechanisms Underlying Inhibition Of Inflammatmentioning

confidence: 99%

Bioactive dietary peptides and amino acids in inflammatory bowel disease

Zhang

Kovacs-Nolan

et al. 2014

Amino Acids

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“…Intriguingly, several small peptides, some comprising only three residues, have been shown to be effective in the treatment of experimental colitis in mice (7)(8)(9)(10)(11). One example is a tripeptide (MC-12) derived from annexin A1, a calcium-dependent phospholipid-binding, anti-inflammatory protein (12).…”

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confidence: 99%

An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease

Caceres

Bansal

Navarro

et al. 2017

Journal of Biological Chemistry

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Edited by Wolfgang PetiInflammatory bowel diseases (IBDs) are a set of complex and debilitating diseases for which there is no satisfactory treatment. Recent studies have shown that small peptides show promise for reducing inflammation in models of IBD. However, these small peptides are likely to be unstable and rapidly cleared from the circulation, and therefore, if not modified for better stability, represent non-viable drug leads. We hypothesized that improving the stability of these peptides by grafting them into a stable cyclic peptide scaffold may enhance their therapeutic potential. Using this approach, we have designed a novel cyclic peptide that comprises a small bioactive peptide from the annexin A1 protein grafted into a sunflower trypsin inhibitor cyclic scaffold. We used native chemical ligation to synthesize the grafted cyclic peptide. This engineered cyclic peptide maintained the overall fold of the naturally occurring cyclic peptide, was more effective at reducing inflammation in a mouse model of acute colitis than the bioactive peptide alone, and showed enhanced stability in human serum. Our findings suggest that the use of cyclic peptides as structural backbones offers a promising approach for the treatment of IBD and potentially other chronic inflammatory conditions. Inflammatory bowel diseases (IBDs)3 are a set of chronic inflammatory disorders of the gastrointestinal tract; the two major forms are ulcerative colitis and Crohn's disease (1). Although there are several medications on the market for IBD, they generally only provide temporary relief, and 70% of IBD patients require surgical intervention (2). Because the current treatments are not satisfactory, new drug leads are being sought from a range of sources, including small molecules from plants and bioactive regions of larger proteins (3-6).Intriguingly, several small peptides, some comprising only three residues, have been shown to be effective in the treatment of experimental colitis in mice (7-11). One example is a tripeptide (MC-12) derived from annexin A1, a calcium-dependent phospholipid-binding, anti-inflammatory protein (12). Annexin A1 mediates expression of cytokines such as TNF-␣, IL-6, and IL-10. It is required for the inhibition of NF-B activity by anti-inflammatory drugs (13) and has recently been shown to be a potential biomarker of therapeutic efficacy for IBD (14). The N-terminal region of annexin A1 comprising residues 2-26 (Ac2-26) has been well studied (15, 16) and appears to have the same biological effects as the full-length protein (17). Analysis of a series of peptides based on the N-terminal sequence of annexin A1 showed that MC-12 (Ac-Gln-Ala-Trp) was the most potent inhibitor of NF-B activity in SW480 cells (13).Small peptides such as MC-12 are likely to be unstable and not viable drug leads, supported by the finding that high doses (25 mg/kg) of MC-12 were required to elicit an in vivo response in mouse colitis models, and it was more effective when injected compared with oral administration (18). Improving t...

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“…KPV encapsulated in polysaccharide for release primarily in the colon may reduce inflammatory mucosal changes [39] . Similarly, a PepT1transportable soy tripeptide VPY reduced intestinal inflammation, suggesting its use as a possible treatment for infla mmatory bowel disease [40] . Recently, it has been hypothesized that different microbial genomes within the intestinal tract may play a role in the immune response in several inflammatory diseases [41] .…”

Section: Peer-reviewmentioning

confidence: 99%

Clinical relevance of intestinal peptide uptake

Freeman

2015

WJGPT

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AIM:To determine available information on an independent peptide transporter 1 (PepT1) and its potential relevance to treatment, this evaluation was completed. METHODS:Fully published English language literature articles sourced through PubMed related to protein digestion and absorption, specifically human peptide and amino acid transport, were accessed and reviewed. Papers from 1970 to the present, with particular emphasis on the past decade, were examined. In addition, abstracted information translated to English in PubMed was also included. Finally, studies and reviews relevant to nutrient or drug uptake, particularly in human intestine were included for evaluation. This work represents a summary of all of these studies with particular reference to peptide transporter mediated assimilation of nutrients and pharmacologically active medications.

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The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation

Cited by 153 publications

References 50 publications

Bioactive dietary peptides and amino acids in inflammatory bowel disease

Bioactive dietary peptides and amino acids in inflammatory bowel disease

An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease

Clinical relevance of intestinal peptide uptake

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