Hypertension is the leading preventable cause of premature death worldwide. In Asia, the prevalence of hypertension is growing faster than in other parts of the world. It is a chronic condition that can often increase the risk of stroke, diabetes mellitus, chronic kidney, and heart problems as the leading causes of death. The growth rate of hypertension is 18% in women and 25% in men and increases to 47% at age ≥60 years. Angiotensin I converting enzyme (ACE; dipeptidyl carboxypeptidase, EC18.104.22.168) plays a significant role in regulating blood pressure.
The enzyme can hydrolyze angiotensin I into an angiotensin II vasoconstrictor and deactivate the bradykinin vasodilator. Inhibition of ACE activity is considered a critical therapeutic approach to treat hypertension. There are ACE-inhibitors such as captopril, enalapril, lisinopril, and ramipril for hypertension treatment in humans. However, these synthetic drugs have several side effects, such as dry cough, skin rashes, and angioneurotic edema. Thus, the development of safe and natural ACE inhibitors is needed for future treatment and to prevent hypertension, one of which comes from the potential of fisheries and marine resources through bioactive peptides.
Bioactive peptides are increasingly becoming an important thing, starting points for drug development in the pharmaceutical field. Among the various bioactive antihypertensive peptides have been widely studied, and the mechanism of their activity involves the inhibition of the angiotensin I (ACE) converting enzyme, the key enzyme responsible for regulating blood pressure through the renin-angiotensin system. ACE inhibitors are an alternative way of therapy for hypertension, heart failure, and diabetic nephropathy. Peptides derived from food proteins are considered safer and easier to absorb compared to synthetic drugs. C-terminal residues from ACE inhibitory peptides play a significant role in competitive binding to active ACE locations. The most dominant and potential waste is aromatic or hydrophobic amino acids in its C-terminal.
Biologically active peptide is made of (a) enzymatic hydrolysis by digestive enzymes, (b) food processing, (c) proteolysis by enzymes derived from microorganisms or plants. In many studies, a combination of (a) and (b) or (a) and (c) has sufficient evidence in the production of functional peptides. Several sources of bioactive peptides are known to have a biological activity such as soybean as an antioxidant, corn as an ACE inhibitor, whey milk as an osteoblast proliferation, β-casein as an anti-inflammatory and tuna as an ACE inhibitor.
Marine organisms produce several sources of functional ingredients such as bioactive peptides, enzymes, polyunsaturated fatty acids (PUFAs), vitamins, minerals, phenolic phlorotannins, and polysaccharides. Besides, marine organisms promise excellent prospects for industrial development such as pharmaceuticals, cosmetics, chemicals, nutritional supplements, and therapeutic agents. Natural inhibitors from fisheries and marine are believed to have no side effects, are safer and healthier when compared to synthetic drugs. In recent years, research on the potential of fisheries and marine as an ACE inhibitor has been extensively studied, ranging from soft-shelled turtle, fermented mackerel, sardine muscle, Alaskan Pollack skin, marine shrimp, salmon chum, yellowfin, collagen squid skin, Spirulina platensis, and Chlorella Vulgaris.
Author: Dwi Yuli Pujiastuti
Pujiastuti, DY; Amin, MNG; Alamsjah, MA; Hsu, J.-L. Marine Organisms as Potential Sources of Bioactive Peptides that inhibit the Activity of Angiotensin I-Converting Enzymes: A Review. Molecules 2019 , 24, 2451-2466.