Skip to main content
SpringerLink
Log in

Conclusions and Future Perspectives

  • Chapter
  • First Online:
Opioid Food Peptides

  • 151 Accesses

Abstract

Food-derived exorphins are usually 4–20 amino acid peptides released from food proteins like caseins, whey, gluten, RuBisCo, β-conglycinin, and albumin. They are generated through gastrointestinal digestion, simulated gastrointestinal digestion (SGID), or fermentation. They show structural features that enable them to bind opioid receptors (μ, δ, and κ). These opioid receptors are distributed widely in the central and peripheral nervous system, gastrointestinal tract, some immune cells, and other tissues. These exorphins may act as agonists or antagonists for these opioid receptors. They play various physiological roles in gastrointestinal motility, analgesia, anxiolysis, emotional and behavior development, memory consolidation, blood pressure regulation, prolactin secretion, food and fat intake, hormone release, appetite, and mucous formation. Moreover, these exorphins are correlated with the development of various physiological complications. The conventional opioids show numerous side effects and thereby limit the clinical effectiveness. Food-derived exorphins are safe alternatives for the pharmaceutical and food industry. The merits include oral consumption and bioavailability, safety due to a lack of side effects, and activation at the endogenous opioid receptors. Therefore, these peptides have enough scope in the food and pharmaceutical industry for the development of functional foods and nutraceuticals. Moreover, deeper research with explored signal cascade mechanisms at the cellular and molecular level is needed to explore food exorphins as therapeutic mediators, functional foods, or nutraceuticals for human health promotion.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Artemova NV, Bumagina ZM, Kasakov AS et al (2010) Opioid peptides derived from food proteins suppress aggregation and promote reactivation of partly unfolded stressed proteins. Peptides 31(2):332–338

    CAS  PubMed  Google Scholar 

  • Barati M, Yousefi M, Ebrahimi-Mameghani M (2017) Oryzatensin-stimulated PBMCs increase cancer progression in-vitro. Iran J Allergy Asthm 16(2):120–126

    Google Scholar 

  • Belem MA, Gibbs BF, Lee BH et al (1999) Proposing sequences for peptides derived from whey fermentation with potential bioactive sites. J Dairy Sci 82(3):486–493

    CAS  PubMed  Google Scholar 

  • Brandt W, Barth A, Höltje HD (1994) Investigations of structure-activity relationships of β-casomorphins and further opioids using methods of molecular graphics. In: Brantl V, Teschemacher H (eds) β-casomorphins and related peptides: recent developments. Wiley, Weinheim, pp 93–104

    Google Scholar 

  • Brantl V, Teschemacher H, Henschen A et al (1979) Novel opioid peptides derived from casein (beta-casomorphins). I. Isolation from bovine casein peptone. Hoppe Seylers Z Physiol Chem 360(9):1211–1216

    CAS  PubMed  Google Scholar 

  • Brantl V, Teschemacher H, Blasig J et al (1981) Opioid activities of beta-casomorphins. Life Sci 28(17):1903–1909

    CAS  PubMed  Google Scholar 

  • Brantl V, Pfeiffer A, Herz A et al (1982) Antinociceptive potencies of beta-casomorphin analogs as compared to their affinities towards mu and delta opiate receptor sites in brain and periphery. Peptides 3(5):793–797

    CAS  PubMed  Google Scholar 

  • Cade R, Privette R, Fregly M et al (2000) Autism and schizophrenia: intestinal disorders. Nutr Neurosci 3:57–72

    CAS  PubMed  Google Scholar 

  • Chiang T, Sansuk K, Van Rijn RM (2016) Beta-arrestins 2 dependence of delta opioid receptor agonists is correlated with alcohol intake. Br J Pharmacol 173:323–343

    Google Scholar 

  • Chiba H, Tani F, Yoshikawa M (1989) Opioid antagonist peptides derived from κ-casein. J Dairy Res 56:363–366

    CAS  PubMed  Google Scholar 

  • Choi J, Sabikhi L, Hassan A, Anand S (2012) Bioactive peptides in dairy products. Int J Dairy Technol 65(1):1–12

    CAS  Google Scholar 

  • Cieslinska A, Kaminski S, Kostyra E et al (2007) β-Casomorphin-7 in raw and hydrolyzed milk derived from cows of alternative β-casein genotypes. Milchwissenschaft 62:125–127

    CAS  Google Scholar 

  • Day A, Freer R, Liao C (1981) Morphiceptin (beta-casomorphin (1-4) amide): a peptide opioid antagonist in the field stimulated rat vas deferens. Res Commun Chem Pharmacol 34(3):543–546

    CAS  Google Scholar 

  • De Noni I (2008) Release of beta-casomorphins 5 and 7 during simulated gastro-intestinal digestion of bovine beta-casein variants and milk-based infant formulas. Food Chem 110(4):897–903

    PubMed  Google Scholar 

  • De Noni I, Cattaneo S (2010) Occurrence of b-casomorphins 5 and 7 in commercial dairy products and in their digests following in vitro simulated gastro-intestinal digestion. Food Chem 119:560–566

    Google Scholar 

  • Dorian B (2009) Use of a peptide as a therapeutic agent. PCT/EP2008/007842

    Google Scholar 

  • Dubynin VA, Malinovskaya IV, Belyaeva YA (2008) Delayed effect of exorphins on learning of albino rat pups. Biol Bull 35:43–49

    CAS  Google Scholar 

  • Fanciulli G, Dettori A, Tomasi PA et al (2002) Prolactin and growth hormone response to intracerebroventricular administration of the food opioid peptide gluten exorphin B5 in rats. Life Sci 71(20):2383–2390

    CAS  PubMed  Google Scholar 

  • Fanciulli G, Dettori A, Fenude E et al (2003) Intravenous administration of the food-derived opioid peptide gluten exorphin B5 stimulates prolactin secretion in rats. Pharmacol Res 47(1):53–58

    CAS  PubMed  Google Scholar 

  • Fanciulli G, Dettori A, Demontis MP et al (2004) Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier. Life Sci 76(15):1713–1719

    PubMed  Google Scholar 

  • Fanciulli G, Dettori A, Demontis MP et al (2005) Serum prolactin levels after administration of the alimentary opioid peptide gluten exorphin B4 in male rats. Nutr Neurosci 7(1):53–55

    Google Scholar 

  • Fukudome S, Yoshikawa M (1992) Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett 296(1):107–111

    CAS  PubMed  Google Scholar 

  • Fukudome S, Yoshikawa M (1993) Gluten exorphin C. A novel opioid peptide derived from wheat gluten. FEBS Lett 316(1):17–19

    CAS  PubMed  Google Scholar 

  • Fukudome S, Jinsmaa Y, Matsukawa T (1997) Release of opioid peptides, gluten exorphins by the action of pancreatic elastase. FEBS Lett 412(3):475–479

    CAS  PubMed  Google Scholar 

  • Gritsaĭ OB, Dubynin VA, Bespalova ZD et al (2009) Effects of several exorphins and endorphins on the escape reaction of the cockroach Periplaneta Americana under elevated temperature conditions. Zh Evol Biokhim Fiziol 45(4):391–407

    PubMed  Google Scholar 

  • Hamel U, Kielwein G, Teschemacher H (1985) Beta-casomorphin immunoreactive materials in cows' milk incubated with various bacterial species. J Dairy Res 52(1):139–148

    CAS  PubMed  Google Scholar 

  • Hirata H, Sonoda S, Agui S et al (2007) Rubiscolin-6, a δ opioid peptide derive from spinach RuBisCo, has anxiolytic effect via activating σ1 and dopamine D1 receptors. Peptides 28(10):1998–2003

    CAS  PubMed  Google Scholar 

  • Jinsmaa Y, Takenaka Y, Yoshikawa M (2001) Designing of an orally active complement C3a agonist peptide with anti-analgesic and anti-amnesic activity. Peptides 22(1):25–32

    CAS  PubMed  Google Scholar 

  • Johnsen LB, Rasmussen LK, Petersen TE et al (1994) Characterization of three types of human alpha s1-casein mRNA transcripts. Biochem J 309:237–242

    Google Scholar 

  • Kairupan TS, Cheng KC, Asakawa A (2019) Rubiscolin-6 activates opioid receptors to enhance glucose uptake in skeletal muscle. J Food Drug Anal 27(1):266–274

    CAS  PubMed  Google Scholar 

  • Kaminski S, Cieoelinska A, Kostyra E (2007) Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet 48(3):189–198

    PubMed  Google Scholar 

  • Kaneko K, Iwasaki M, Yoshikawa M et al (2010) Orally administered soymorphins, soy-derived opioid peptides, suppress feeding and intestinal transit via gut μ1-receptor coupled to 5-HT1A, D2, and GABAB systems. Am J Physiol Gastrointest Liver Physiol 299(3):799–805

    Google Scholar 

  • Kaneko K, Mizushige T, Miyazaki Y et al (2014) δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice. Am J Physiol Regul Integr Comp Physiol 306(4):265–272

    Google Scholar 

  • Koch G, Wiedemann K, Teschemacher H (1985) Opioid activities of human β-casomorphins. Arch Pharmacol 331(4):351–354

    CAS  Google Scholar 

  • Kong X, Zhou H, Hua Y et al (2008) Preparation of wheat gluten hydrolysates with high opioid activity. Eur Food Res Technol 227(2):511–517

    CAS  Google Scholar 

  • Korhonen H, Pihlanto A (2006) Bioactive peptides: production and functionality. Int Dairy J 16(9):945–960

    CAS  Google Scholar 

  • Kostyra E, Sienkiewicz-Szapka E, Jarmolowska B et al (2004) Opioid peptides derived from milk proteins. Pol J Food Nutr 13(54):25–35

    CAS  Google Scholar 

  • Liebmann C, Barth A, Neubert K et al (1986) Effects of β-Casomorphin on 3h-ouabain binding to guinea-pig heart membranes. Pharamzie 41:670–671

    CAS  Google Scholar 

  • Martínez-Maqueda D, Miralles B, De Pascual-Teresa S et al (2012) Food-derived peptides stimulate mucin secretion and gene expression in intestinal cells. J Agric Food Chem 60(35):8600–8605

    PubMed  Google Scholar 

  • Matar C, Goulet J (1996) β-casomorphin 4 from milk fermented by a mutant of Lactobacillus helveticus. Int Dairy J 6(4):383–397

    CAS  Google Scholar 

  • Meisel H, FitzGerald RJ (2000) Opioid peptides encrypted in intact milk protein sequences. Br J Nutr 84(1):27–31

    Google Scholar 

  • Mitsumoto Y, Sato R, Tagawa N et al (2019) Rubiscolin-6, a δ-opioid peptide from spinach rubisco, exerts antidepressant-like effect in restraint-stressed mice. J Nutr Sci Vitaminol 65(2):202–204

    CAS  PubMed  Google Scholar 

  • Miyazaki Y, Kaneko K, Iguchi S (2014) Orally administered δ opioid agonist peptide rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance. Mol Nutr Food Res 58(10):2046–2052

    CAS  PubMed  Google Scholar 

  • Morley JE, Levine AS, Yamada T et al (1983) Effect of exorphins on gastrointestinal function, hormonal release, and appetite. Gastroenterology 84(6):1517–1523

    CAS  PubMed  Google Scholar 

  • Muehlenkamp MR, Warthesen JJ (1996) Beta-casomorphins: analysis in cheese and susceptibility to proteolytic enzymes from Lactococcus lactis ssp Cremoris. J Dairy Sci 79(1):20–26

    CAS  PubMed  Google Scholar 

  • Mullally MM, Meisel H, FitzGerald RJ (1997) Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a tryptic fragment of bovine b-lactoglobulin. FEBS Lett 402:99–101

    CAS  PubMed  Google Scholar 

  • Nurminen ML, Sipola M, Kaarto H et al (2000) α-Lactorphin lowers blood pressure via radiotelemetry in normotensive and spontaneously hypertensive rats. Life Sci 66:1535–1543

    CAS  PubMed  Google Scholar 

  • Ohinata K, Agui S, Yoshikawa M (2007a) Soymorphins, novel μ opioid peptides derived from soy β-conglycinin β-subunit, have anxiolytic activities. Biosci Biotechnol Biochem 71(10):2618–2621

    CAS  PubMed  Google Scholar 

  • Ohinata K, Agui S, Yoshikawa M (2007b) Soymorphins, novel μ opioid peptides derived from soy β-conglycinin β-subunit, have anxiolytic activities. Biosci Biotechnol Biochem 71(10):2618–2621

    CAS  PubMed  Google Scholar 

  • Pandey M, Kapila S, Kapila R et al (2018) Evaluation of the osteoprotective potential of whey derived-antioxidative (YVEEL) and angiotensin-converting enzyme inhibitory (YLLF) bioactive peptides in ovariectomised rats. Food Funct 9(9):4791–4801

    CAS  PubMed  Google Scholar 

  • Patten GS, Head RJ, Abeywardena MY (2011) Effects of casoxin 4 on morphine inhibition of small animal intestinal contractility and gut transit in the mouse. Clin Exp Gastroenterol 4:23–31

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pert CB, Snyder SH (1973) Opiate receptor: demonstration in nervous tissue. Science 179(4077):1011–1014

    CAS  Google Scholar 

  • Pihlanto-Leppälä A (2000) Bioactive peptides derived from bovine whey proteins. Trends Food Sci Technol 11:347–356

    Google Scholar 

  • Raies MH, Kapila R, Kapila S (2015) Release of β-casomorphin-7/5 during simulated gastrointestinal digestion of milk β-casein variants from Indian crossbred cattle (Karan fries). Food Chem 1(168):70–79

    Google Scholar 

  • Robins MT, Chiang T, Mores KL et al (2018) Critical role for Gi/o-Protein activity in the dorsal striatum in the reduction of voluntary alcohol intake in C57Bl/6 Mice. Front Psych 9:112

    Google Scholar 

  • Rokka T, Eeva-Liisa S, Jari T et al (1997) Release of bioactive peptides by enzymatic proteolysis of Lactobacillus GG fermented UHT milk. Milchwissenschaft 52:675–678

    CAS  Google Scholar 

  • Schieber A, Brückner H (2000) Characterization of oligo-and polypeptides isolated from yoghurt. Eur Food Res Technol 210(5):310–313

    CAS  Google Scholar 

  • Schusdziarra V, Henrichs I, Holland A (1981) Evidence for an effect of exorphins on plasma insulin and glucagon levels in dogs. Diabetes 4:362–364

    Google Scholar 

  • Sienkiewicz-Szłapka E, Jarmołowska B, Krawczuk S et al (2009) Contents of agonistic and antagonistic opioid peptides in different cheese varieties. Int Dairy J 19(4):258–263

    Google Scholar 

  • Sipola M, Finckenberg P, Korpela R et al (2002) Effect of long-term intake of milk products on blood pressure in hypertensive rats. J Dairy Res 69:103–111

    CAS  PubMed  Google Scholar 

  • Stuknytė M, Maggioni M, Cattaneo S et al (2015) Release of wheat gluten exorphins A5 and C5 during in vitro gastrointestinal digestion of bread and pasta and their absorption through an in vitro model of intestinal epithelium. Food Res Int 72:208–214

    Google Scholar 

  • Takahashi M, Moriguchi S, Yoshikawa M et al (1994) Isolation and characterization of oryzatensin: a novel bioactive peptide with ileum-contracting and immunomodulating activities derived from rice albumin. Biochem Mol Biol Int 33(6):1151–1158

    CAS  PubMed  Google Scholar 

  • Takahashi M, Fukunaga H, Kaneto H et al (2000) Behavioral and pharmacological studies on gluten exorphin A5, a newly isolated bioactive food protein fragment, in mice. Jpn J Pharmacol 84(3):259–265

    CAS  PubMed  Google Scholar 

  • Tani F, Iio K, Chiba H et al (1990) Isolation and characterization of opioid antagonist peptides derived from human lactoferrin. Agric Biol Chem 54(7):1803–1810

    CAS  PubMed  Google Scholar 

  • Teschemacher H, Koch G, Brantl V (1997) Milk protein-derived opioid receptor ligands. Biopolymers 43(2):99–117

    CAS  PubMed  Google Scholar 

  • Udenigwe CC, Adebiyi AP, Doyen A et al (2012) Low molecular weight flaxseed protein-derived arginine-containing peptides reduced blood pressure of spontaneously hypertensive rats faster than amino acid form of arginine and native flaxseed protein. Food Chem 132:468–475

    CAS  PubMed  Google Scholar 

  • Yang S, Yunden J, Sonoda S et al (2001) Rubiscolin, a δ selective opioid peptide derived from plant RuBisCo. FEBS Lett 509(2):213–217

    CAS  PubMed  Google Scholar 

  • Yang S, Kawamura Y, Yoshikawa M (2003) Effect of rubiscolin, a δ opioid peptide derived from RuBisCo, on memory consolidation. Peptides 24(2):325–328

    CAS  PubMed  Google Scholar 

  • Yoshikawa M, Tani F, Ashikaga T et al (1986) Purification and characterization of an opioid antagonist from a peptide digest of bovine κ-casein. Agric Biol Chem 50:2951–2954

    CAS  Google Scholar 

  • Yoshikawa M, Tani F, Shiota H et al (1994) Casoxin D, an opioid antagonist ileum-contracting/vasorelaxing peptide derived from human αs1-casein. In: Brantl V, Teschemacher H (eds) β-Casomorphins and related peptides: recent developments. Wiley, Weinheim, pp 43–48

    Google Scholar 

  • Yoshikawa M, Takahashi M, Yang S (2003) Delta opioid peptides derived from plant proteins. Curr Pharm Des 9(16):1325–1330

    CAS  PubMed  Google Scholar 

  • Zioudrou C, Streaty RA, Klee WA (1979) Opioid peptides derived from food proteins. J Biol Chem 254(7):2446–2449

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Sri Pratap College, Cluster University Srinagar, Srinagar, Jammu and Kashmir, India

    Mohammad Raies Ul Haq

Authors
  1. Mohammad Raies Ul Haq
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2020 The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ul Haq, M.R. (2020). Conclusions and Future Perspectives. In: Opioid Food Peptides. Springer, Singapore. https://doi.org/10.1007/978-981-15-6102-3_9

Download citation

Publish with us

Policies and ethics

Search

Navigation