Bioactive lead compounds and molecular targets for the treatment of heart diseases

Abstract

Cardiovascular disease (CVD) is a group of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CADs) that are recognized as heart including angina attack and myocardial infarction. CVD is responsible for about 31.5% of all global deaths. About 92 million US adults suffer from CVD; this is expected to rise higher per the adult population by 2030 owing to augmentation in obesity and diabetes disorders, and consequently, healthcare services are overwhelmed with a huge load [1]. According to the World Health Organization (WHO), 2016 [2],morethan18million individuals lose their life annually from CVD and 1.1 billion adults recorded increased blood pressure. Many of these people have been exposed to unhealthy lifestyle, tobacco habits, eating foods with high salt, and deficiency in physical practice. CVDis usually accompanied by atherosclerosis and an increased risk of blood clots. Other organs, heart, kidneys, brain, and eyes, might also be damaged in response to arteries injury. Therefore, CVD is regarded as a complex disease that results from the consequence of multiple pathogenic factors, which reflects the different interactions of many interconnected genes and their relevant products [3]. Chronic proatherogenic inflammation is one of the main causes of CVDs and its supplementary severe complications. Endoplasmic reticulum (ER) is an important organelle for folding, releasing, and synthesizing secretory and transmembrane proteins. Any pathological stimuli such as hypoxia, ischemia, inflammation, and oxidative stress can change the homeostatic function of ER, and this results in the aggregation of unfolded proteins, a phenomena denoted as ER stress. This unfolded protein response, UPR (a complex signaling network), is triggered by ER stress. Massive investigations revealed that ER stress is one of the crucial phases in the progress of various CVDs such as heart failure, ischemic heart disease, and atherosclerosis. Many pharmacological therapeutics are available for treating CVDs; however, the present drugs cause many adverse effects such as renal failure, rhabdomyolysis, and hemorrhagic with prolonged use. Natural products have always been regarded as a valuable source for the discovery of new drugs [4]. Drugs or those obtained from animals, plants, or microorganisms have a great role in human healthcare. They have recorded massive diversities chemically and pharmacologically. The drugs approved by the FDA constitute more than 50% natural products or derivatives [