Plant Peptides and Health: How Plant Peptides Unlock Optimal Health

The quest toward optimal health moves in tandem with breakthroughs in nutrition science. Much of today’s nutritional research interests revolve around the gut microbiome, inflammation, and metabolic health. Carving out a space of their own in the field are bioactive peptides.

Aside from serving as nutrients, proteins in foods can wield positive effects on human health, such as antioxidant, immunomodulatory, antimicrobial, and mineral binding functions.^1,2,3,4 This article will delve into how cells recognize and use peptides to unlock optimal health. We’ll also explore why plant peptides are just as powerful — if not more — than those from animal sources.

The Game of Enzymes: Understanding How Peptides Work

Peptides in foods are encrypted in their parent proteins, where they lie inactive until released. When you eat food containing the parent protein, the digestive enzymes in your gut — such as trypsin, pepsin, and pancreatin — randomly liberate (and thereby activate) the peptides.

The breakdown of proteins into peptides depends upon your body’s ability to produce the necessary enzymes in the right quantities. Those that are cut down to the right size (smaller tends to be better) then rely on the overall health of your digestive tract to be absorbed and put to use.

Once free from their confines, peptides are able to wield their effects in your body. To do so, they imitate natural signaling molecules (ligands) in your body by binding to receptors, the gatekeepers of your cells. These proteins, often located on the surface of your cells, serve as checkpoints that control the transit of substances and information into and out of the cell. Your cells can have many types of receptors depending on its function.

To understand how peptides and receptors work, think of a “lock and key” system. As shown in the image below, only the right size peptide (“key”) that closely matches the active site (“keyhole”) of a receptor (“lock”) can bind to it. The better the match, the tighter the binding and the more potent the effects.

(source: https://tisserandinstitute.org/cleaning-receptors-myth/)

Many types of receptors exist on your cells, each with a specialized function or activity. In general, upon binding of a peptide, a receptor can either directly produces or transmits a signal that leads to a change inside a cell. It’s these effects that excite scientists — depending on their amino acid sequence (or how they are cut and configured), peptides affect major body systems, including the immune, cardiovascular, digestive, and nervous systems. And they’re not limited to just one function either!⁵

Getting to the Sequence of the Matter

Not all peptides can bind to every receptor, and not all have the same effects. Structure is important when talking about proteins and peptides; and in this regard, we’re talking about the amino acid sequence of the peptides.

While researchers are still learning exactly how a peptide’s structure affects its function, we do know that the amino acid sequence of a peptide governs its activity. Continuing with the “lock and key” analogy from above, the unique sequence is like the shape of a key that unlocks a specific door (receptor).

For example, the presence of the following amino acids may contribute to a peptide’s antioxidant activity:^6,7

• Leucine
• Methionine
• Proline
• Valine
• Tryptophan
• Tyrosine

Several of these amino acids are found in rich amounts in sorghum and millet proteins.⁸

Another valuable amino acid sequence is valine-alanine-proline, produced by sourdough fermentation of wheat. According to research studies, this epitope (the part of the peptide that interacts with the receptor) possesses the ability to block angiotensin-converting enzyme (ACE), thereby keeping a tight control over blood pressure.⁹

More ACE-inhibiting peptides have been identified in Ginkgo biloba seeds, wheat, peas, mushrooms, walnuts, bitter melon seeds, and spinach.^10,11

The Bioavailability of Plant Peptides

Traditionally, peptide research has centered largely around those sourced from animals, such as meat, milk, and eggs. But further research into how collagen peptide supplements are made turn many people away. (And no, there are no vegan collagen peptides).

If you’re looking for alternatives to collagen peptide supplements that can provide the same benefits, there’s good news: plant peptides. Scientists are quickly learning that plant peptides are in a league of their own when it comes to health benefits.

One standout feature of plant peptides is their bioavailability. For your body to use peptides, they must be able to survive enzyme degradation so that they can cross the gut barrier to enter the bloodstream. In fact, protein peptides can encounter over 40 different digestive enzymes as it passes through your digestive tract.¹² But many plant peptides — especially proline-rich peptides — are able to resist degradation by enzymes, giving them a better chance at absorption.¹³

The ease of absorption also largely depends on the size, chemical properties, and charge of the peptides, with smaller peptides having a much easier time than larger ones.¹⁴ Here again, we can see plant peptides having the upper hand. That’s because even if plant and animal proteins have similar structures, plant proteins are smaller (and therefore easier to absorb).¹⁵

Are plant peptides particularly well-suited for human cell receptors? Several proposals support this question. Researchers have noted that important bioactive peptides in plants, such as an insulin-like peptides in spinach and alfalfa, existed 1 billion years ago.^16,17,18 According to one proposal, the abundance of plant peptides with bioactivities in the human body suggests a close evolutionary relationship.¹⁸ This makes plant peptides the ideal keys to unlocking important receptors.

Additionally, emerging evidence shows that the non-protein content of plants — such as polyphenols, dietary fibers, and other carbohydrates — actually enhance the bioavailability of health-optimizing plant peptides.^13,19 Polyphenols, for example, can protect protein peptides from enzymes and assist their absorption by binding to receptors that influence transport across the gut lining.²⁰ These are features only available in plants!

Plant Peptides Optimize Your Health

We now have strong evidence that plant peptides can fulfill our health needs. Let’s look at the latest research on how plant peptides can help you unlock optimal health.

1. Regulate Cellular Health

Abnormal cellular activity can lead to many health issues, including cancer, inflammation, autoimmune diseases, and metabolic problems. Cancer and heart disease continue to be leading causes of death in industrialized countries, and new preventive and treatment options are desperately needed.²¹

Treatments for cells that dysfunction often cause complications and serious side effects. Many conventional treatments have low specificity, which means they can harm healthy cells while trying to manage the troublemakers. It is an important and rapidly growing area of research to find more targeted therapies that only modulate sick cells while not interrupting the healthy ones. This critical need has fueled the massive growth in peptide research.

Plant peptides are the next generation of cell- and receptor-specific therapies.

Lunasin, a peptide isolated from legumes, has been shown to induce apoptosis (cell death) in various unhealthy cell types.^22,23,24 Arginine-rich peptides like lunasin are capable of penetrating heavily guarded cells in a matter of minutes, making them promising delivery vehicles for bioactive molecules into cells.^25,26 In a fascinating study involving melanoma cells, lunasin specifically targeted newly transformed cancer cells and was able to change their phenotype to a non-cancerous one.²⁷

Many other plant-derived peptides have also displayed anticancer activities in laboratory and animal studies.^28,29

2. Mimic Cellular Messengers

Emerging research suggests plant peptides may open up new horizons for prevention and treatment and many health concerns.

Various plants, like spinach, alfalfa, moringa and the leaves of oat plants contain peptides that mimic insulin activity.^30,31,32 One study, which reviewed the effects of flaxseed peptide fractions in diabetic mice, found that the peptides decreased blood glucose levels by up to 69%. Another study identified leginsulin, a peptide found in high concentrations in Asian legumes, as another insulin-like peptide that could lower blood glucose.³⁴

Plant peptides can also inhibit several enzymes involved in metabolic disorders, such as alpha-glucosidase, alpha-amylase, dipeptidyl peptidase-IV, and glucose transporter systems.

3. Delay Progression of Chronic Illnesses

Plant peptides may be able to help by controlling inflammation, one of the main features of chronic joint, kidney, brain, and heart disease.^36,37,38 In one study, rats with chronic kidney disease who ingested plant derived peptides and lactic acid had a reduction of inflammatory markers. The combination of lactic acid and fermented peptides also significantly protected mice kidneys from further damage.³⁹

Your kidneys are a part of your body’s detox system. They remove waste and extra fluid, maintaining a healthy balance of minerals so that your body can continue functioning properly. Chronic kidney disease — or the gradual failure of your kidneys — means waste, fluid, and minerals can build up to dangerous levels in your body.

➤ Want to learn more about the power of plant peptides? Check out 10 Benefits of Plant Peptides.

The Source of Peptides Matters!

While popular, animal-derived protein sources have several limitations and concerns.
If consumed in large amounts, animal protein is usually accompanied by saturated fat that can aggravate metabolic diseases.⁴⁰ Animal proteins are also associated with ethical, ecological and quality issues, like instability and contamination.

Even with safety checks throughout the process, the presence of harmful substances can never be fully ruled out in animal-derived products. Some animals may carry unconventional, or not yet identified, infections. And while the rendering process may reduce the number of microbes, it may not remove or inactivate certain infectious agents. And the methods may not clear them completely especially if the infection is severe.⁴¹

The good news is there are alternatives to collagen peptide supplements. Plants grown under stringent, careful conditions are free of pathogens, pollutants, and other toxic contaminants. Compared to their counterparts, plant peptides are safer and better tolerated.

Plant Peptides are the Future

An enormous amount of new and emerging science is focused on the benefits of plant peptides. It is not surprising that although relatively new, the global peptide therapeutics market is valued at about $23 million in 2020 and is expected to more than double in the next 5 years.⁴² Plant peptides are poised to revolutionize the pharma, supplement and beauty industries. Innovative plant peptides can elevate the function of plant proteins and provide more targeted benefits.

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References

¹ Sánchez A, Vázquez A. Bioactive peptides: A review. Food Quality and Safety. 2017;1(1):29-46. https://academic.oup.com/fqs/article/1/1/29/4791729?login=true

² Chakrabarti S, Jahandideh F, Wu J. Food-derived bioactive peptides on inflammation and oxidative stress. Biomed Res Int. 2014;2014:608979. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914560/

³ Rutherfurd-Markwick KJ. Food proteins as a source of bioactive peptides with diverse functions. Br J Nutr. 2012;108(Suppl 2):149-157. https://pubmed.ncbi.nlm.nih.gov/23107526/

⁴ Chakrabarti S, Guha S, Majumder K. Food-Derived Bioactive Peptides in Human Health: Challenges and Opportunities. Nutrients. 2018;10(11):1738. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265732/

⁵ Meisel H, Fitzgerald RJ. Biofunctional peptides from milk proteins: Mineral binding and cytomodulatory effects. Current Pharmaceutical Design. 2003;9(16):1289-1295. https://www.ingentaconnect.com/content/ben/cpd/2003/00000009/00000016/art00006

[1] Sarmadi BH, Ismail A. Antioxidative peptides from food proteins: A review. Peptides. 2010;31(10);1949-1956. https://www.sciencedirect.com/science/article/abs/pii/S0196978110002640

[1] Chen HM, Muramoto K, Yamauchi F. Structural Analysis of Antioxidative Peptides from Soybean β-Conglycinin. J Agric Food Chem. 1995;43(3):574-578. https://pubs.acs.org/doi/pdf/10.1021/jf00051a004

[1] Duodu KG, Awika JM. Chapter 8 – Phytochemical-Related Health-Promoting Attributes of Sorghum and Millets. Sorghum and Millets (Second Edition): Chemistry, Technology and Nutritional Attributes. 2019:225-258. https://www.sciencedirect.com/science/article/pii/B9780128115275000083#bib127 [1] Rizzello CG, Cassone A, Di Cagno R, Gobbetti M. Synthesis of Angiotensin I-Converting Enzyme (ACE)-Inhibitory Peptides and γ-Aminobutyric Acid (GABA) During Sourdough Fermentation by Selected Lactic Acid Bacteria. J Agric Food Chem. 2008;56(16):6936-6943. https://pubs.acs.org/doi/pdf/10.1021/jf800512u

[1] Ma FF, Wang H, Wei CK, Thakur K, Wei ZJ, Jiang L. Three Novel ACE Inhibitory Peptides Isolated From Ginkgo biloba Seeds: Purification, Inhibitory Kinetic and Mechanism. Front Pharmacol. 2019;9:1579. https://www.frontiersin.org/articles/10.3389/fphar.2018.01579/full

[1] Daskaya-Dikmen C, Yucetepe A, Karbancioglu-Guler F, Daskaya H, Ozcelik B. Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants. Nutrients. 2017;9(4):316. Published 2017 Mar 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409655/

[1] Pérez-Gregorio R, Soares S, Mateus N, de Freitas V. Bioactive Peptides and Dietary Polyphenols: Two Sides of the Same Coin. Molecules. 2020;25(15):3443. Published 2020 Jul 29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435807/

[1] Karami Z, Akbari-Adergani B. Bioactive food derived peptides: a review on correlation between structure of bioactive peptides and their functional properties. J Food Sci Technol. 2019;56(2):535-547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400753/

[1] Amigo L, Hernández-Ledesma B. Current Evidence on the Bioavailability of Food Bioactive Peptides. Molecules. 2020;25(19):4479. Published 2020 Sep 29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582556/ [1] Ramírez-Sánchez O, Pérez-Rodríguez P, Delaye L, Tiessen A. Plant Proteins Are Smaller Because They Are Encoded by Fewer Exons than Animal Proteins. Genomics Proteomics Bioinformatics. 2016;14(6):357-370. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5200936/

[1] Collier E, Watkinson A, Cleland CF, Roth J. Partial purification and characterization of an insulin-like material from spinach and Lemna gibba G3. J Biol Chem. 1987;262(13):6238-6247. https://pubmed.ncbi.nlm.nih.gov/3553187/

[1] Morley JE, Meyer N, Pekary AE, et al. A prolactin inhibitory factor with immunocharacteristics similar to thyrotropin releasing factor (TRH) is present in rat pituitary tumors (GH3 and W5), testicular tissue and a plant material, alfalfa. Biochem Biophys Res Commun. 1980;96(1):47-53. https://www.sciencedirect.com/science/article/pii/0006291X80911791?via%3Dihub

[1] Patil SP, Goswami A, Kalia K, Kate AS. Plant-Derived Bioactive Peptides: A Treatment to Cure Diabetes. Int J Pept Res Ther. 2020;26(2):955-968. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223764/

[1] Ten Have GAM, van der Pijl PC, Kies AK, Deutz NEP. Enhanced Lacto-Tri-Peptide Bio-Availability by Co-Ingestion of Macronutrients. PLOS ONE. 2015;10(6):e0130638. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130638

[1] Martel F, Monteiro R, Calhau C. Effect of polyphenols on the intestinal and placental transport of some bioactive compounds. Nutrition Research Reviews. 2010;23(1):47-64. https://www.cambridge.org/core/journals/nutrition-research-reviews/article/effect-of-polyphenols-on-the-intestinal-and-placental-transport-of-some-bioactive-compounds/8BDAAD43B214A5F1FD4FF4217AC4E370 [1] National Cancer Institute. Cancer Statistics. 2020. https://www.cancer.gov/about-cancer/understanding/statistics

[1] Jeong HJ, Jeong JB, Kim DS, de Lumen BO. Inhibition of Core Histone Acetylation by the Cancer Preventive Peptide Lunasin. J Agric Food Chem. 2007;55(3):632-637. https://pubs.acs.org/doi/10.1021/jf062405u

[1] González-Montoya M, Cano-Sampedro E, Mora-Escobedo R. Bioactive Peptides from Legumes as Anticancer Therapeutic Agents. Int J Cancer Clin Res. 2017;4(2):081. https://clinmedjournals.org/articles/ijccr/international-journal-of-cancer-and-clinical-research-ijccr-4-081.php?jid=ijccr

[1] de Mejia EG, Wang W, Dia VP. Lunasin, with an arginine-glycine-aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3. Mol Nutr Food Res. 2010;54(3):406-414. https://pubmed.ncbi.nlm.nih.gov/19937853/

[1] Nakase I, Konishi Y, Ueda M, Saji H, Futaki S. Accumulation of arginine-rich cell-penetrating peptides in tumors and the potential for anticancer drug delivery in vivo. J Control Release. 2012;159(2):181-188. https://pubmed.ncbi.nlm.nih.gov/22285548/

[1] de Lumen BO. Lunasin: a cancer-preventive soy peptide. Nutr Rev. 2005;63(1):16-21. https://pubmed.ncbi.nlm.nih.gov/15730231/

[1] Shidal C, Al-Rayyan N, Yaddanapudi K, Davis KR. Lunasin is a novel therapeutic agent for targeting melanoma cancer stem cells. Oncotarget. 2016;7(51):84128-84141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356649/

[1] González-Montoya M, Hernández-Ledesma B, Silván JM, Mora-Escobedo R, Martínez-Villaluenga C. Peptides derived from in vitro gastrointestinal digestion of germinated soybean proteins inhibit human colon cancer cells proliferation and inflammation Food Chemistry. 2018;242(1):75-82. https://www.sciencedirect.com/science/article/pii/S0308814617314917?casa_token=0yFjMo3ngU8AAAAA:AC9AQn4zfIQxf_zwuS7FIKjYDdAg4BDfTMqk9RbeMEreel0OUzxZiAsX6MLDmPVBGptAtyW1Jx0 [1] Fang EF, Hassanien AAE, Wong JH, Bah CSF, Soliman SS, Ng TB. Isolation of a new trypsin inhibitor from the Faba bean (Vicia faba cv. Giza 843) with potential medical applications. Protein Pept Lett. 2011;18(1):64-72. https://pubmed.ncbi.nlm.nih.gov/20955169/

[1] Patil SP, Goswami A, Kalia K, Kate AS. Plant-Derived Bioactive Peptides: A Treatment to Cure Diabetes. Int J Pept Res Ther. 2020;26(2):955-968. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223764/

[1] Paula PC, Oliveira JTA, Sousa DOB, Alves BGT, Carvalho AFU, Franco OL, Vasconcelos IM. Insulin-like plant proteins as potential innovative drugs to treat diabetes – The Moringa oleifera case study. N Biotechnol. 2017;39(Part A):99-109. https://www.sciencedirect.com/science/article/abs/pii/S1871678416324608

[1] Costa IS, Medeiros AF, Piuvezam G, Medeiros GCBS, Maciel BLL, Morais AHA. Insulin-Like Proteins in Plant Sources: A Systematic Review. Diabetes Metab Syndr Obes. 2020;13:3421-3431. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533237/

[1] Doyen A, Udenigwe CC, Mitchell PL, Marette A, Aluko RE, Bazinet L. Anti-diabetic and antihypertensive activities of two flaxseed protein hydrolysate fractions revealed following their simultaneous separation by electrodialysis with ultrafiltration membranes. Food Chem. 2014;145:66-76. https://pubmed.ncbi.nlm.nih.gov/24128450/

[1] Hashidume, T., Sakano, T., Mochizuki, A. et al. Identification of soybean peptide leginsulin variants in different cultivars and their insulin-like activities. Sci Rep 8, 16847 (2018). https://www.nature.com/articles/s41598-018-35331-5

[1] Patil et al. 2020. (see reference #25)

[1] Mohammad Shahi M, Rashidi MR, Mahboob S, Haidari F, Rashidi B, Hanaee J. Protective effect of soy protein on collagen-induced arthritis in rat. Rheumatol Int. 2012;32(8):2407-2414. https://pubmed.ncbi.nlm.nih.gov/21681567/

[1] Wu S, Bekhit AELD, Wu Q, Chen M, Liao X, Wang J, Ding Y. Bioactive peptides and gut microbiota: Candidates for a novel strategy for reduction and control of neurodegenerative diseases. Trends in Food Science & Technology. 2021;108:164-176. https://www.sciencedirect.com/science/article/pii/S0924224420307391?dgcid=rss_sd_all

[1] Okagu IU, Ndefo JC, Aham EC, Obeme-Nmom JI, Agboinghale PE, Aguchem RN, Nechi RN, Lammi C. Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits. Nutrients. 2021; 13(9):3266. https://www.mdpi.com/2072-6643/13/9/3266/htm# [1] He LX, Abdolmaleky HM, Yin S, Wang Y, Zhou JR. Dietary Fermented Soy Extract and Oligo-Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota. Nutrients. 2020;12(8):2376. Published 2020 Aug 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468970/

[1] Nehete JY, Bhambar RS, Narkhede MR, Gawali SR. Natural proteins: Sources, isolation, characterization and applications. Pharmacogn Rev. 2013;7(14):107-116. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841988/

[1] Scientific Steering Committee. Scientific Opinion on the Risks of Non-Conventional Transmissible Agents, Conventional Infectious Agents or Other Hazards Such as Toxic Substances Entering the Human Food or Animal Feed Chains Via Raw Material From Fallen Stock and Dead Animals (Including Also: Ruminants, Pigs, Poultry, Fish, Wild/Exotic/Zoo Animals, Fur animals, Cats, Laboratory Animals and Fish) or Via Condemned Materials. 1999. https://ec.europa.eu/food/system/files/2020-12/sci-com_ssc_out53_en.pdf [1] Coherent Market Insights. Peptide Therapeutics Market Analysis. 2020. https://www.coherentmarketinsights.com/market-insight/peptide-therapeutics-market-1837