Role of food-derived opioid peptides in the central nervous and gastrointestinal systems

Abstract

Opioid receptors are widely distributed in central nervous system and peripheral tissues. Endogenous opioid receptor ligands are involved in many physiological processes.Exogenous peptides, derived from food proteins with gastrointestinal proteases, also exert opioid-like activities, and they include gluten exorphins (wheat), casomorphins (milk), rubiscolins (spinach), and soymorphins (soybean). Milk-derived opioid peptides play both agonistic and antagonistic roles, and most of the opioid peptides exert regulatory functions in the central nervous system, related to nociception, emotion and memory after oral, intracerebroventricular, or intraperitoneal administration. This indicates that the peptides may have crossed the blood-brain barrier or acted peripherally.Furthermore, some food-derived opioid peptides influence gastrointestinal functions such as gut motility, hormone release, appetite, mucus production, and local immunity. In healthy states, food-derived opioid peptides could benefit both the nervous and digestive systems, whereas in pathological conditions, the gastrointestinal permeability change and opioid excess may contribute to pathogenesis of some disorders. Practical applicationsOpioid receptors are important biological targets for the treatment of multiple diseases. Traditional opiate compounds, such as alkaloids, are demonstrated to exert numerous side effects, thereby limiting their clinical effectiveness. It is thought that food-derived opioid peptides may be safer than the alkaloids, and therefore can be applied in functional food development. In this review, we summarized the already discovered food opioid peptides from different sources, and elaborated their physiological functions on the central nervous and gastrointestinal systems. These effects support further exploration of the opioid peptides as therapeutic agents or as functional food ingredient for human health promotion. K E Y W O R D Scasomorphins, central nervous system, exorphins, food peptides, gastrointestinal tract, opioid peptides, rubiscolins, soymorphins

Novel Opioids: Systematic Web Crawling Within the e-Psychonauts’ Scenario

“…Finally, it is interesting to note that a range of both endogenous (e.g., amphibian opioid peptides such as dermorphins and deltorphins) and food-derived (e.g., derivatives from milk and soya such as soymorphines and β-casomorphins) opioid peptides, possessing low levels of potency (Teschemacher et al, 1997;Negri et al, 2000;Ohinata et al, 2007;Liu and Udenigwe, 2018), were not mentioned in psychonaut fora.…”

Artificial intelligence identified peptides modulate inflammation in healthy adults

“…38 Moreover, foodderived opioid peptides may be involved in the regulation of inflammatory processes. 39 Intestinal Mu opioid receptors are well described as responding to peptides in their opioid function and a variety of other functionalities including hormonelike, analgesia, and anti-hypertensive effects. 40 Peptides from bovine, casein and soy protein were characterized for their functionality.…”

Bioactive peptides from food fermentation: A comprehensive review of their sources, bioactivities, applications, and future development

“…Studies have revealed that opioid peptides derived from animal proteins bind to µ‐opioid peptide receptors and those obtained from plant proteins bind to δ‐opioid peptide receptors (Yoshikawa et al., 2005), except for soymorphins that bind to µ‐opioid peptide receptors, due to their nature of receptor selectivity (Liu & Udenigwe, 2019; Ohinata et al., 2007). Various studies showed that opioid peptides could be isolated from milk (Fan et al., 2019; Hafeez et al., 2014), yogurt (Papadimitriou et al., 2007), kefir (Ebner et al., 2015), cheese (Nguyen et al., 2015), whey (Pihlanto‐Leppälä, 2000; Yadav et al., 2015), wheat (Garg et al., 2018), amaranth grain (Tovar‐Pérez et al., 2019), soybean (Liu & Udenigwe, 2019), meat (Udenigwe & Howard, 2013), and fish and shellfish (Harnedy & FitzGerald, 2012). It has been shown that these food‐derived exogenous opioid peptides could exert agonistic activity that is comparable to that of endogenous ligands, whereas the antagonistic peptides could exert inhibitory effects similar to naloxone, a potent drug that has antagonistic effect on opiate receptor (Hartmann & Meisel, 2007).…”