One of the drawbacks of the antihypertensive drugs therapy is the high cost and the undesired side effects. Therefore, alternatives are highly recommended because of the low cost and very little adverse effects (9). Numerous biological bioactive peptides have been isolated from dairy products after the processing of these products with digestive enzymes or by fermentation. Bioactive peptides have been categorized according to their pharmacological action, such as opioids, anti-hypertensive, anticoagulants, metal binding protein, and immune-regulative agents (10). Numerous peptides and protein that have been extracted from natural food products have an ACE inhibitory activity and can be efficient substitutes for chemical antihypertensive drugs. A dairy product like cheese contains seven kinds of antihypertensive peptides, revealed after the cheese was treated with protease K (11-13). Moreover, it has been reported that Gouda cheese contains 4 types of antihypertensive peptides (14). Animal studies showed that fermentation of milk by Lactobacillus helveticus CPN4 produced natural antihypertensive peptide which has a notable blood pressure lowering activity on the induced hypertensive rats (15, 16, 17) and human models (18). Recently, a new kind of food product, called Food for Specified Health Uses, has been developed in Japan and become available in markets around the county. These kinds of products have been certified by the Japanese Ministry of Health, Labor and Welfare. However, about eight categories of ACE-inhibitory peptides have been added to these food products. In addition, two out of eight of these ACE-inhibitory peptides are milk derivative peptides (19). Inhibition of the ACE is the most effective known mechanism of the natural polypeptide (20).
Although natural bioactive peptides are not as potent as the synthetic ones, their side effects are much more diminished or lacking than the synthetic antihypertensive drugs. There are many natural antihypertensive peptides derived from food proteins, such as casein, whey, ovalbumin, red algae, soy, gelatin, chicken muscle, dried bonito, corn, sardines, rapeseed, potato, chick pea, tuna muscle, pea albumin, garlic, wheat germ, sake, porcine haemoglobin and squid (21). However, these polypeptides are activated by the action of protease enzymes, specifically pepsin, trypsin, and chymotrypsin in the gastrointestinal tract.
Another mechanism of action underlying the antihypertensive property of the natural polypeptide is the inhibition of renin, which catalyzes the conversion of angiotensinogen prohormone to angiotensin I. Peptides derived from flaxseed and pea protein have potential inhibitory activity of renin and ACE (22) (see Fig-1)