Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

Gleeson, John P.; Heade, Joanne; Ryan, Sinéad M.; Brayden, David J.

doi:10.1016/j.peptides.2015.05.009

Cited by 36 publications

(42 citation statements)

References 40 publications

(43 reference statements)

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“…73 Isolated ex vivo intestinal tissue from rat and human has been tested with PEs in Ussing chambers, [74][75][76] as well as in everted rat gut sacs. 77 Although these systems account for villi, increased transporter expression and mucus secretion, they lack blood supply which assists complete mechanistic repair of damaged tissue.…”

mentioning

confidence: 99%

Safety concerns over the use of intestinal permeation enhancers: A mini-review

2016

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Intestinal permeation enhancers (PEs) are key components in »12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo-and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co-absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy.

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confidence: 99%

Safety concerns over the use of intestinal permeation enhancers: A mini-review

2016

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“…Sodium caprate, a medium‐chain fatty acid surfactant, decreased the TEER of isolated rat jejunal tissue and increased the permeability of FITC‐labelled tripeptides (Gleeson et al . ). Chassaing et al .…”

Section: Dietary Factors and The Intestinal Barriermentioning

confidence: 97%

Diet, food components and the intestinal barrier

Gleeson

2017

Nutrition Bulletin

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The majority of dietary nutrient absorption occurs in the small intestine, with the intestinal epithelium acting as a barrier to the contents of the intestinal lumen. This barrier is maintained by intestinal epithelial cells, which support nutrient uptake but prevent translocation of bacteria, allergens and toxins. There is complex signalling and interaction between intestinal epithelia, macrophages, luminal contents and the microbiota which can modulate epithelial paracellular porosity. Intake of alcohol, fatty acids, pharmaceuticals and pathogenic bacteria has been reported to increase paracellular permeability, increase production of pro‐inflammatory cytokines and temporarily reorganise tight junctional proteins. Conversely, numerous probiotics, nutraceuticals and food‐derived bioactive components are promising due to reported restoration of intestinal barrier integrity by increasing production of anti‐inflammatory cytokines and increased expression of tight junctional proteins. In vitro co‐culture models exist and recent advances in microfluidic in vitro models are promising tools for investigating the complex effect of dietary components on the intestinal barrier. Temporarily perturbing the intestinal barrier may increase the oral bioavailability of therapeutic molecules. However, people with impaired intestinal integrity (e.g. those with Crohn's, coeliac or ulcerative colitis disease) should avoid foods which further perturb barrier integrity, while increasing intake of specific foods and possibly probiotics to promote intestinal barrier restoration.

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“…Furthermore, systemic availability showed XPP (X refers to Val, Ile, and Leu) in a meal in the presence of other macronutrients had a prolonged portal bioavailability of 0.2% to 0.3% (Ten Have et al, 2015); in addition, the permeation of IPP could be enhanced by the medium chain fatty acids (Gleeson, Heade, Ryan, & Brayden, 2015). Danish, Vozza, Byrne, Frias, and Ryan (2017) formulated IPP and leu-Lys-Pro (LKP) into a chitosan nanoparticle to improve permeation.…”

Section: The Bioavailability Of Ipp and Vppmentioning

confidence: 99%

Preparation, Bioavailability, and Mechanism of Emerging Activities of Ile‐Pro‐Pro and Val‐Pro‐Pro

Zheng

et al. 2019

Comp Rev Food Sci Food Safe

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Ile‐Pro‐Pro and Val‐Pro‐Pro are two most well‐known food‐derived bioactive peptides, initially identified as inhibitors of angiotensin I‐converting enzyme (ACE) from a sample of sour milk. These two peptides were identified in fermented and enzymatic hydrolyzed cow and non‐cow (that is, goat, sheep, buffalo, yak, camel, mare, and donkey) milk, as well as sourdough prepared from wheat, rye, and malt. Similar to other bioactive peptides, bioavailability of these peptides is low (about 0.1%), reaching picomolar concentration in human plasma; they showed blood pressure lowering activity in animals and in human, via improved endothelial function, activation of ACE2, and anti‐inflammatory property. Emerging bioactivities of these two peptides toward against metabolic syndrome and bone‐protection received limited attention, but may open up new applications of these peptides as functional food ingredients. Further studies are warranted to determine the best source as well as to identify novel enzymes (particularly from traditional fermented milk products) to improve the efficiency of production, to characterize possible peptide receptors using a combination of omics technology with molecular methods to understand if these two peptides act as signal‐like molecules, to improve their bioavailability, and to explore new applications based on emerging bioactivities.

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Stability, toxicity and intestinal permeation enhancement of two food-derived antihypertensive tripeptides, Ile-Pro-Pro and Leu-Lys-Pro

Cited by 36 publications

References 40 publications

Safety concerns over the use of intestinal permeation enhancers: A mini-review

Safety concerns over the use of intestinal permeation enhancers: A mini-review

Diet, food components and the intestinal barrier

Preparation, Bioavailability, and Mechanism of Emerging Activities of Ile‐Pro‐Pro and Val‐Pro‐Pro

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