Bioactive peptides and proteins: An auspicious class of nutraceuticals By Solomon Ojigbo

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A ‘nutraceutical’ is any nontoxic food-derived supplement that has scientifically-proven health benefits for both the treatment and prevention of disease. This term was coined in 1989 by Stephen DeFelice. Nutraceuticals may range from isolated nutrients, dietary supplements to genetically engineered food, herbal products, and processed products such as cereals, and beverages.

The growing interest in nutraceuticals reflects the awareness of consumers about epidemiological studies indicating that a specific diet or component of the diet is associated with a lower risk for a certain disease. A typical example is seen in the French paradox which drew the attention of researchers, in which low incidence of cadiovascular disease was observed in the french population associated with red wine consumption, but having a greater amount of saturated fat in their average diet than in other countries.

In recent years, proteins and peptides have gained prominence as potential source of nutraceuticals. Many studies have shown that peptides from various food sources possess bioactivities, including antihypertensive, antioxidant, anticancer, antimicrobial, and opioid activities as well as immuno-modulatory and cholesterol-lowering properties, suggesting their potential use as nutraceuticals for health promotion and disease risk reduction.

Peptides are short polymers of amino acids linked together by peptide bonds. One or more polypeptide subunits makeup a protein molecule. Proteins are essential components of tissues in living organisms and participate in a large number of physiological processes within cells. In foods, proteins are an important macronutrient, serving as a source of energy and amino acids, which are essential for normal growth and maintenance of the body functions. The physiological and functional properties of food proteins are attributed to peptides with biological activities, released from their precursor proteins during gastrointestinal digestion or food processing.

Such peptides with biological activities are referred to as bioactive peptides. Bioactive peptides are specific protein fragments with hormone or drug like activity that eventually modulate physiological function through binding interactions to specific receptors on target cells leading to induction of physiological responses. The activity of these peptides is dependent on their amino acid composition and sequence. Moreover, some peptides are multifunctional and can exert more than one effect mentioned. Most of the dietary peptides having biological activity which have been investigated to date originated from milk. Examples include immunoglobulins, caseins, whey proteins etc. However, proteins from other animal sources, as well as plant proteins, have been reported to exert specific bioactivities.

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The first biologically active peptide found in milk was opioid peptides followed by the immunomodulatory peptides.

 Anticancer activity

Bioactive proteins and peptides have been associated in preventing the development of different types of cancer. Soybean Kunitz trypsin inhibitor, was reported by Kobayashi et al in 2004 to suppress ovarian cancer cell invasion by blocking urokinase activity. Bowman Birk protease inhibitor (BBI), a water-soluble protein isolated from legumes and many monocotyledonous seeds, has shown anticarcinogenic activity in in vitro and in vivo studies and is now intensively studied as a cancer chemopreventive agent in clinical trials. Lunasin, a 43 amino acid peptide is a novel chemopreventive agent from soybean, and has been found to suppress chemical carcinogen and viral oncogene-induced transformation of mammalian cells and inhibit skin carcinogens in mice.

 Cholesterol-lowering effect

Many proteins and their peptides are known to exert a cholesterol-lowering effect, among which soybean is the most well-recognised source of hypocholesterolemic proteins and peptides and soybean-rich diet has become the most potent dietary tool for treating hypercholesterolemia. An early study by Sirtori et al. in 1977 have reported that 7S globulin, a major storage protein in soybean, decreased plasma cholesterol concentration by 35 per cent in rats. Recent studies have shown that soy protein reduces circulation of triacylglycerols and cholesterol in hypercholesterol individuals. Proteins from soybean given to animals or human subjects by oral administration are subjected to protease digestion in the gastrointestinal tract, releasing the bioactive peptides which inhibit cholesterol absorption.

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 Antihypertensive activity

Antihypertensive peptides have been found effective in treating and preventing hypertension primarily by inhibiting the angiotensin-converting enzyme (ACE), which is mainly responsible for  the regulation of blood pressure and maintenance of the equilibrium of water and salts in the body (electrolyte homeostasis). ACE is also responsible for the inactivation of the vasodilator bradykinin, which in turn leads to increase in blood pressure. ACE acts by converting the peptide angiotensin I with 10 amino acid residue into angiotensin II with 8 amino acid residue. Angiotensin II is a potent vasoconstrictor which also has a regulatory effect on cellular lipoxygenases and catalyses the oxidation of low-density lipoprotein (LDL), a process implicated in atherogenesis. Antihypertensive peptides can decrease the activity of ACE and indirectly reduce the level of angiotensin II, thereby exerting a vasorelaxing effect on blood vessels. Examples of Antihypertensive peptides include Lactoglobulin, Lactalbumin, αs1-Casein and β-casein which are derived from milk and Ovalbumin derived from egg.

 Antimicrobial activity

A broad spectrum of antimicrobial peptide protects the gastrointestinal tract against pathogenic bacteria and viruses. A typical example of peptide with antimicrobial activity is Lactoferricin, formed from Lactoferrin an iron-binding glycoprotein during digestion. lactoferrin is responsible for inhibition of growth of pathogens by iron scavenging.

Antimicrobial peptides are also of immense importance for their potential application in food preservation and for therapeutic use in health care. Bioactive peptides have been identified in a wide variety of natural sources from microorganisms to animals and plants. Antimicrobial peptides display inhibitory effects against microbe-caused food deterioration. Advantages of antimicrobial peptides over chemical preservatives include better selectivity and sensitivity on target microorganisms, fewer adverse effects introduced to the food, lower intensity of heat treatment required, and retaining of organoleptic and nutritional properties of food, such as less acidic and lower salt content.

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 Immunomodulatory properties

Immunomodulating peptides have been detected in human as well as in cow milk proteins. From human milk protein digests, two peptides, β-casein and α-lactalbumin enhance the phagocytic activity of macrophages both in mice and humans and enhance resistance against certain bacteria in mice. Immunomodulating peptides have also been found to stimulate the proliferation of human lymphocytes, the phagocytic activities of macrophages and antibody synthesis. The peptides may stimulate the proliferation and maturation of T cells and natural killer cells for defence of  infants against a large number of bacteria, particularly enteric bacteria.

References

Kobayashi H., Suzuki M., Kanayama N., & Terao T. (2004) Clin. Exp. Metastasis 21, 159–166

FitzGerald R. and Murray B. (2006). Bioactive peptides and lactic fermentations. International Journal of Dairy Technology, 59, 118-125.

Shrikant S., Raghvendar S, Shashank R. (2011). Bioactive Peptides: A Review. Int. J. Bioautomation, 15(4), 223-250.

Shahidi F. & Zhong Y. (2008). Bioactive Peptides. Journal of AOAC International vol. 91, no. 4

Sirtori, C.R., Agradi, E., Mantero, O., Conti, F., & Gatti, E. (1977) Lancet 1, 275–277

Tapas A, Sakarkar D and Kakde R (2008). Flavonoids as Nutraceuticals: A Review. Tropical Journal of Pharmaceutical Research, 7 (3): 1089-1099

Walther B, Sieber R. (2011). Bioactive proteins and peptides in foods. International Journal for Vitamin and Nutrition Research 81(2-3):181-92. DOI: 10.1024/0300-9831/a000054

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