Peptides Promote Health

PEPTIDES ISOLATED from food products could aid in the fight against ailments and diseases ranging from high blood pressure to cancer. That's the take-home message delivered by several speakers at a symposium presented before the Division of Agricultural & Food Chemistry during last month's American Chemical Society national meeting in Salt Lake City.

These bioactive peptides are believed to deliver health benefits beyond the nutritional value of their component amino acids, and research into such compounds is hot right now, according to Jianping Wu, an assistant professor in the department of agricultural, food, and nutritional science at the University of Alberta, in Edmonton. Foods and food-derived products that offer such benefits are known as functional foods or nutraceuticals.

Wu's group is studying one such food product: ovotransferrin, an iron-binding glycoprotein found in egg whites. Previous research suggested that the protein might have antioxidant activity. Antioxidants are desirable because oxidation is a major factor in the onset and development of many chronic diseases, including cardiovascular disease, diabetes, and cancer, Wu explained. He said his research is intended to "develop a functional food ingredient from proteins that can be used for the prevention or treatment of chronic disease."

Wu and his team wanted to find out whether particular peptide segments within ovotransferrin offer some exceptional antioxidant activity. It's difficult to break apart or digest the protein with protease enzymes, Wu told C&EN. But after trying "a whole bunch" of methods, he found one that efficiently released the peptides that he'd predicted would have biological activity. Wu says he can't provide further details because he is in the process of patenting the technique.

After using the method to break down ovotransferrin, Wu tested the antioxidant activity of the released peptides. He was surprised to find that their antioxidant activity as a group was more than 10 times higher than that of the intact ovotransferrin protein and was comparable with that of some of the most active antioxidants derived from fruits and vegetables.

The results represent the first evidence that potent antioxidant peptides can be produced from ovotransferrin, Wu said.

He next purified and determined the structure of two of the most potent ovotransferrin peptides, each of which contains only three amino acids. These short peptides have a good chance of easily passing from the digestive tract into the bloodstream, Wu said, so "the possibility for these peptides to have health benefits in vivo looks very promising."

But does the digestive tract release these particular peptides when a person eats an egg? Wu is trying to find out. He has conducted some initial studies by simulating the human gut, complete with the digestive enzymes pepsin and pancreatin. Digestion of ovotransferrin in this simulated gut system produced a mixture of peptides with strong antioxidant activity. Wu said further study will be needed to "determine if digestion of cooked egg might release some interesting antioxidant peptides."

OVER AT the University of Illinois, Urbana-Champaign, researchers are studying peptides derived from soybeans, a food that is reputed to have several health benefits. Elvira de Mejia, an associate professor of food science and human nutrition, noted that the Food & Drug Administration permits manufacturers to put a claim on food labels stating that eating 25 g/day of soy protein may reduce the risk of heart disease. This benefit, along with soy's reputed anticancer properties, are believed by many to derive from the food's anti-inflammatory activity, de Mejia said.

For her part, she set out to determine the contribution of soy peptides to the suppression of inflammation. Using chromatography and filtration, de Mejia and her team extracted and purified peptides that are naturally present in soybeans. They then focused on three of those peptides: lunasin, which is a 43-amino acid molecule, and two similar peptides.

In an assay using immune cells known as macrophages, de Mejia found that all three peptides showed anti-inflammatory activity (Food Chem. 2009, 114, 108). The peptides lowered the cells' production of nitric oxide and prostaglandins and reduced their expression of iNOS, an enzyme that produces nitric oxide, and COX-2, an enzyme that makes prostaglandins. Both iNOS and COX-2 are involved in the body's inflammation pathway.

Unlike some nonselective anti-inflammatory COX inhibitors such as aspirin and ibuprofen, the soy peptides have no impact on COX-1, an enzyme that helps protect the stomach lining and kidneys, de Mejia told C&EN. It should be noted, however, that some selective inhibitors of COX-2, such as Vioxx, have been taken off the market after showing serious side effects, including an increased risk for stroke and heart attack.

If the soy peptides can avoid such side effects, de Mejia's results suggest that lunasin in particular might be useful in reducing inflammation. And inflammation, she noted, "is considered a central pathway for different chronic diseases such as obesity, cardiovascular disease, and even cancer."

De Mejia recently reported that lunasin could be detected in the blood plasma of men who ate 50 g/day of soy protein in the form of a soy-milk shake and a chili dish prepared from canned soybeans (J. Agric. Food Chem. 2009, 57, 1260). That observation shows that consumption of ordinary soy products can release enough lunasin in the body to inhibit inflammation, de Mejia said. "That doesn't mean if you eat soy today and you don't eat it for the rest of the month, you will get those benefits," she told C&EN. But she thinks that consuming the equivalent of three soy-milk shakes per week might be sufficient.

BEYOND the bioactive peptides, soybeans' high fiber and protein content make them an even more attractive food, noted de Mejia, who drinks soy milk and finds soybean chili very tasty. She added that other researchers have shown that soy proteins such as β-conglycinin reduce body fat and body weight.

Like soy products, oats are also recognized for their health benefits. FDA allows manufacturers to note on food labels that the soluble fiber found in oats can reduce the risk of heart disease. Eunice C. Y. Li-Chan, a professor of food, nutrition, and health at the University of British Columbia, in Vancouver, wants to know whether oats offer other health benefits.

In particular, Li-Chan said she is studying oat-derived peptides that, at least in vitro, have shown the ability to suppress angiotensin I-converting enzyme (ACE), a key regulator of blood pressure. Suppressing the enzyme lowers blood pressure.

Her work with oats has its origins in a seemingly unrelated food—fermented fish. Manufacturers market a product in Japan and North America that contains peptides isolated from fermented bonito fish. These peptides can lower blood pressure by inhibiting ACE activity. Li-Chan found that the fermentation step wasn't necessary and that she could produce peptides with ACE-inhibitor activity by using enzymes to hydrolyze raw fish such as Pacific whiting or hake (J. Agric. Food Chem. 2008, 56, 410).

Li-Chan realized that vegetarians or consumers with seafood allergies might not want to eat a fish-derived product. So she began examining plant proteins as a source of peptides similar to those she had isolated from fish.

One potential source was oats. Some food processors separate the carbohydrate fraction from oats to obtain its soluble β-glucan component, which is then added to other foods to enhance their cholesterol-lowering ability. But Li-Chan was curious about the potential of the leftover protein fraction from the oats, which is currently fed to farm animals or discarded.

USING PROTEOMICS TOOLS, she determined that the 11S globulin protein from oats contains amino acid sequences matching ones reported in the literature to be capable of inhibiting ACE. She then tracked down an enzyme—food-grade thermolysin—that would cleave the protein at the correct sites to release the desired peptide sequences. Using this enzyme, Li-Chan told C&EN, she has now produced "quite potent peptide preparations." These peptides could be concentrated and then consumed either in the form of a dietary supplement or as an ingredient in functional foods, she added.

Consumers could conceivably obtain some of these peptides by eating oats, she said, but others wouldn't be available because "our digestive enzymes don't cleave the oat protein in exactly the right places to release the active peptide sequences." In addition, the amounts a consumer could derive from eating oats wouldn't be high enough to affect blood pressure, Li-Chan said.

A pill containing her oat peptides "probably wouldn't work for people who have really high blood pressure," Li-Chan said. "It would be more for people who are taking it to maintain healthy blood pressure or to treat borderline or mild hypertension."

Li-Chan believes these food-derived peptides would offer advantages over prescription drugs that are used as ACE inhibitors to reduce blood pressure. Whereas synthetic ACE inhibitors have a range of side effects, including persistent dry cough and retention of potassium, tests with the fish-derived peptides showed no side effects. Li-Chan hopes to test her oat-derived peptides in animal studies and a clinical trial.