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Maize Bioactive Peptides and Their Anti-Cancer Activities

Cancer is one of the leading chronic degenerative diseases in the world. In the recent past, the consumption of wholegrain cereals and some of their derivatives have been attributed to the low risks of various forms of cancer. Peptides, amino acids, and proteins happen to be the main biomolecules in cereals. These biomolecules are available in different quantities within the grains, with the peptides believed to possess various nutraceutical properties that can be exploited for their biological effects in promoting good health, and preventing various forms of cancer.

Legumes such as soybeans, have undergone a variety of extensive studies due to their potential as a great source of bioactive proteins and peptides because they naturally exhibit a higher natural protein content of up to 40%. Cereals such as barley, wheat, maize, and rye have also been studied and marked as potential new sources of bioactive peptides. High quality cereal proteins have always been vital sources of bioactive peptides. They are known to possess distinct amino acid sequences, which if released, can portray a wide range of functionality. For centuries, cereal bioactive peptides have formed a huge part of man’s diet and apart from their nutritional roles, they also have a lot of enviable biological activities.

Maize as a source of bioactive peptides

Maize is a staple food for many countries around the world. Generally, cereals, which maize falls under, are considered as one of the top sources of proteins, vitamins, carbohydrates, and minerals. As far as the human diet goes, wheat, rice, and maize happen to be some of the most important grains in the world, with millions of tones being harvested every year to feed the world’s hungry populations. A typical maize kernel features an embryo, and endosperm, and bran or fiber. The nutrient found in large abundance in maize, is starch. Starch comprises mainly of amylose and amylopectin. This is then followed by proteins that represent about 12% of the total weight of a typical maize kernel.

The content of essential amino acid in maize, is between 5% and 10%, with glutamic acid being the most abundant amino acid in a maize kernel. Also, one kernel of maize has up to four groups of storage proteins comprising of globulins, albumins, glutelins, and prolamins. Globulins and albumins are primarily found in germs, while the other two are predominantly found in the endosperm section of the maize. These four classes are grouped as per their solubility, as follows: albumins are water-soluble; globulins dissolve in salt solutions; prolamins are soluble in alcohol, while glutelins are insoluble in saline solutions or neutral aqueous solutions.

Generally, peptides derived from cereals such as maize have so far been proven to have opiate, antihypertensive, antimicrobial, antioxidant, mineral-binding, anticancer, and antithrombotic properties. In maize, there have been several instances of various bioactive peptides being reported. The bioactive peptides in maize are usually obtained through the process of hydrolysis of the kernels, and from some of the byproducts. Below is a detailed look at some of the top health benefits of maize peptides, and their potential applications as therapies for cancer treatments.

Maize Bioactive Peptides and Their Anti-Cancer Activities

Health Effects & Anticancer Agents of Maize Peptides

The past few years have seen a lot of advances in cereal peptide research, and one major observation that has come out, is the immense health potential of cereal-derived proteins and peptides, including their effects in different stages of cancer. Due to the urgent demand or need for effective therapies for various forms of cancer, chemoprevention has been perceived as one of the most viable approaches for dealing with the prevention, as well as the treatment of cancer. Most of the chemo-preventive agents are perceived to be affordable, safe, and are easily available in large quantities.

Cereal-derived peptides meet these criteria and they are believed to be safer than their synthetic counterparts because they are present in regular human diets, with a wide range of acceptability and availability.

There have been lots of studies that have shown that the anti-cancer potential of peptides, dietary proteins, and amino acids when it comes to regulation, angiogenesis and apoptosis is a vital step towards inhibiting and finally stopping the metastasis of tumor; most of these molecules occur naturally, or they can be easily generated through processes such as fermentation, gastrointestinal digestion, or hydrolysis.

Bioactive peptides portray anti-tumor activities through various mechanisms. The first mechanism of such activities is apoptosis induction. This is a process that features an energy-dependent cascade mediated through certain proteases. It is one of the best strategies that are currently under intense studies to be used as a means of overcoming tumor resistance to certain apoptotic pathways, which usually include the restoration of p53 activity, activation of pro-apoptotic receptors, caspase modulation, as well as proteasome inhibition.

The second mechanism that bioactive peptides exert anti-tumor activities, is through the blockage of intermediate tumor generation. This normally happens through the regulation of certain cellular mechanisms that are associated with the survival and proliferation of the cells, or through biosynthetic pathways that are responsible for controlling the growth of cells.

The third mechanism is through the regulation of immune system functions. This normally happens when the expression of tumor-associated antigens in cancerous cells is increased, by triggering the tumor cells, so that they can release danger signals, which in turn end up stimulating certain proper immune responses or increasing the likelihood of the tumor cells to be easily recognized and killed by the body’s natural immune system.

A vital anticancer effect of maize peptides was demonstrated through the use of in vitro models. With the use of HepG2 cells, it was observed that there was an increase in the rate of apoptotic activities following exposure of the cells to maize peptides obtained through the hydrolysis of proteins got from corn gluten meal.

During that particular in vivo study, the maize peptides were also studied when they were introduced into a H22-tumor-bearing mouse. When these animals were treated with a dose of 400mg/kg of the maize peptides, it was observed that the growth of the tumor was greatly inhibited. Also, when the maize peptide was administered, there was also an enhanced immune system activity compared to the control group, which never received any amount of the maize peptide.

In recent studies conducted in late 2017 by Ortiz-Martinez et al, certain important anti-cancer effects of maize peptides were discovered in HepG2 cells. Fractions of the peptide isolated from Alcalase hydrolysates were found to be stronger than the peptides obtained from the good quality maize. When the HepG2 cells were treated with the fraction of the maize peptides obtained from a variety of maize species, it was observed that there was an increased rate of apoptosis - up to four times. From these results, it was observed that the antiproliferative effects of the peptide fractions had the potential of reducing the antiapoptotic factor expression, offering very promising results about using the maize peptides in the formulation of a variety of anti-cancer treatments.

Maize peptides as antioxidants

One of the main reported activities of maize peptides is their antioxidant capacities. This is primarily due to the presence of very specific amino acids that are known to have radical scavenging effects. Some of these amino acids include tyrosine, histidine, leucine, alanine, proline, phenylalanine, and lysine. There have been several peptides to be identified to have antioxidant activities.
However, the antioxidant potential of these peptides has always been a factor dependent on the enzymatic processes that were used to get them. Studies done in the past suggest that the antioxidant capacity of peptides obtained through processes such as enzymatic hydrolysis had low molecular weights but showed very high potential for antioxidant activities.

Some of the properties of these small peptides include free radical scavenging activities, ion chelating capacity, and the ability to inhibit lipid peroxidation. The antioxidant potential of maize peptides can never be altered by peptides whose origins are total proteins or zein fractions. PH is another factor that is known to affect the antioxidant activity of peptides. For example, native alpha-zein peptides are known to have more antioxidant activity compared to alpha-zein that has been obtained from less acidic or basic environments. Also, synthesized peptides have similar antioxidant activities as these.

It is also worth pointing out that peptides that are smaller than 3kDa have shown very high antioxidant activities in vitro assays in HepG2 cells that have been subjected to very high oxidative stress. Studies also suggest that maize peptides have the potential of increasing the activity of cellular enzymes, and as such, they may portray preventive effects on cell damage as a result of their antioxidant activities. Also, in studies involving macrophage models, it was observed that maize peptides had anti-inflammatory effects.

It is believed that such effects could have been exerted through their anti-oxidative properties. It is known that oxidative stress has the potential of inducing lipid peroxidation, DNA damage, protein oxidation, and ultimately leads to mutant cell proliferation, which then gives way to carcinogenesis. These properties are relevant due to the relationship that exists between oxidative stress and certain degenerative processes, such as carcinogenesis. Hence, the antioxidant properties and activities of maize peptides may prove to be of immense help when it comes to formulating various cancer treatments.

Maize peptides as antihypertensive

Maize peptides have also shown incredible antihypertensive effects. In one of the studies, a peptide with an Ala-Tyr sequence was obtained from a corn gluten meal – this is usually the main by-product of maize wet-milling. This peptide showed immense inhibitory activities when it interacted with the angiotensin I-converting enzyme. The same peptide also displayed antihypertensive activity when it was spontaneously administered in hypertensive rats. In yet another study, it was observed that peptides that were smaller than 3 kDa had high potential for blood pressure reduction when doses of 100mg/kg were administered spontaneously to hypertensive rat models. All of these results are an indication that the molecular weight had an influence in the antihypertensive activity, since peptides that were smaller than 1 kDa showed more activity than peptides that were larger than 3 kDa.

Additionally, the enzymes used in the hydrolysis of the proteins and the peptide generation, also impacted the antioxidant activity of the ensuring peptides. For example, all the peptides obtained from thermolysin and trypsin are some of the most potent, as far as antihypertension is concerned.

Additionally, it was observed that when ultrasonic treatment was applied to corn gluten meal proteins before they underwent the hydrolysis process, there was increased antihypertensive activity in the ensuing peptide. Antihypertensive peptides have so far been isolated and identified as leucine – arginine – proline or simply LRP and leucine – glutamine – proline or simply LQP.

Therefore, the molecular interactions of peptides, as well as their effects on enzymes that can lead to a variety of vascular hemodynamics suggest that these peptides may have potential applications in antihypertensive treatments, though there is a need for further research about this.

Maize enzymes as Hepatoprotective

Past studies suggest that maize peptides also portray a protective effect due to their ability to reduce the damage done to the hepatic tissues. In a study where rats with liver damage caused by exposure to lipopolysaccharides were used as the subjects, it was observed that administering 600mg/kg peptide heavily lowered down the levels of hepatic lesions, cell necrosis, and the levels of the enzymes that are usually indicative of liver damage. During this study, the protective effects of the peptide on the liver were attributed to their antioxidant capacities.

Maize peptides also showed hepatoprotective effects through the facilitation of alcohol metabolism. This can be mainly explained by the presence of leucine that is responsible for maintaining the tricarboxylic acid cycle. The same peptide also displayed anti-apoptotic activities in the liver cells of mice treated with alcohol, as a means of inducing liver damage. A similar study also revealed hepatoprotective effects in mice when doses of 200mg/kg of peptides were administered, leading to a lower concentration of alcohol in the blood. The peptides obtained from maize also showed protective activity against hepatic fibrosis. These studies show the hepatoprotective properties of maize peptides, and this has opened yet another avenue for therapeutic applications of these peptides.

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