Ace enzyme inhibitors
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Angiotensin-Converting Enzyme (ACE) Inhibitors: A Comprehensive Overview
Introduction to ACE Inhibitors
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension and heart-related conditions. They work by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure and alleviating strain on the heart .
Natural ACE Inhibitors from Plants
Plant-Based ACE Inhibitors
Recent research has highlighted the potential of natural ACE inhibitors derived from plants. These natural inhibitors are being explored due to the adverse side effects associated with synthetic ACE inhibitors, such as hypotension, renal insufficiency, and hyperkalaemia. Over 50 plant species have been identified with ACE-inhibitory activity, including Angelica keiskei, Momordica charantia, and Prunus domestica. These plants contain bioactive metabolites like peptides, phenolics, flavonoids, terpenoids, and alkaloids, which not only inhibit ACE but also exhibit antioxidant, antidiabetic, antihyperlipidemic, and anti-inflammatory properties.
Soybean-Derived ACE Inhibitors
Soybean protein isolate (SPI) has also been identified as a source of natural ACE inhibitors. Specific peptides derived from SPI, such as IY and YVVF, have shown significant ACE-inhibitory activity. These peptides maintain their inhibitory properties even after gastrointestinal digestion, making them promising candidates for therapeutic use.
Clinical Applications of ACE Inhibitors
Hypertension and Cardiovascular Diseases
ACE inhibitors are well-established in the treatment of hypertension and various cardiovascular diseases. They reduce systemic vascular resistance without increasing heart rate and promote natriuresis. These inhibitors are effective in reducing mortality in congestive heart failure and left ventricular dysfunction post-myocardial infarction. They also help in stabilizing plaques and preventing ischemic events.
Diabetes and Metabolic Syndrome
ACE inhibitors have shown promise in preventing the onset of type 2 diabetes. Studies indicate that these inhibitors improve insulin sensitivity and glucose metabolism, thereby reducing the incidence of new-onset diabetes by approximately 25% . This makes them particularly beneficial for patients with pre-diabetic conditions such as metabolic syndrome, hypertension, and obesity.
Advances in ACE Inhibitor Design
Domain-Selective Inhibitors
Current ACE inhibitors target both the N- and C-domains of the enzyme, which can lead to side effects like chronic dry cough and angioedema. Recent research aims to develop domain-selective inhibitors that specifically target the C-domain, potentially reducing these side effects while maintaining therapeutic efficacy .
Structural Insights and Rational Drug Design
Advancements in structural biology have provided detailed insights into the enzyme-inhibitor interactions at the active site of ACE. This knowledge facilitates the rational design of next-generation ACE inhibitors that are more effective and have fewer side effects .
Conclusion
ACE inhibitors remain a cornerstone in the treatment of hypertension and cardiovascular diseases. The exploration of natural ACE inhibitors from plants and the development of domain-selective inhibitors represent significant advancements in this field. These innovations promise to enhance the efficacy and safety of ACE inhibitors, offering better therapeutic outcomes for patients with hypertension, diabetes, and related complications.
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