Role of Synthesized Flavonoids as Cardioprotective Prophylactic Agents using in silico in vitro and in vivo models

Abstract

With drastic changes in the life style pattern, increasing number of subjects is at risk of cardiovascular diseases and there is preponderance of evidence for the association of increased oxidative stress with various vascular diseases. These cause premature death from angina, heart attack, stroke, peripheral artery disease, hypertension, ischemia and thrombosis. The loss of control of free-radical formation from the mitochondrion can contribute to the pathology of CVDs through a number of mechanisms including damage to mitochondrial DNA, enzyme degradation, and apoptosis and thus contribute to human disease. Evidence also suggests that oxidases may contribute to ROS generation in the myocardium. In conclusion, the results of the present study, based on their molecular docking scores with ACE, HMG CoA and cholesterol esterase inhibitory activity of the selected compounds were showed excellent results when compared to that of standards captopril, rosuvastatin and simvastatin respectively. The flavonoid compounds showed better binding interactions and docking parameters (binding energy, inhibition constant, intermolecular energy). In vitro the results revealed the potency of synthesized flavonoid compounds for their protection against ACE, HMG CoA and cholesterol esterase enzymes associated with CVDs. All eight synthesized flavonoid compounds showed protective activity when tested for their enzyme inhibitory activities in vitro. The platelet aggregation induced by ADP also exhibited inhibitory effect on platelets to prevent their aggregation and thereby helpful for the prevention and treatment thrombus formation and associated CVD. The in vivo results indicated all three synthesized flavonoid compounds (FA14, FB4 and FC19) exhibited a dose dependent protective activity against isoproterenol-induced MI and established protective effects against oxidative stress caused by free radicals. Therefore these synthesized flavonoids could be a better therapeutic tool for the prevention and treatment of cardiovascular diseases.