Abstract
Recently, cardiovascular disease, also known as loop circulatory system diseases or disorders, is one of the serious diseases including heart disease, stroke, atherosclerosis, myocardial infarction, hypertension, hypotension, and thrombosis. Human pregnane X receptor, PXR, plays a crucial role in exogenous and endobiotic metabolism for rabbit, rat, mouse, and human. The PXR activation can protect the blood vessels from damage of hazardous substances. In this study we aim to investigate the potent lead compounds as PXR receptor agonist against cardiovascular disease. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as PXR agonists from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, bis(4-hydroxybenzyl) ether mono-β-D-glucopyranoside (BEMG), ixerisoside, and tangshenoside II, have displayed higher potent binding affinities than the positive control, PNU-142721, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and PXR protein under dynamic conditions, top TCM compounds, BEMG and tangshenoside II, maintain most of interactions with PXR protein, which keep the ligand binding stable in the binding domain. Hence, we propose BEMG and tangshenoside II as potential lead compounds for further study in drug development process with the PXR protein.
Highlights
Cardiovascular disease, known as loop circulatory system diseases or disorders, is one of the serious diseases including heart disease, stroke, atherosclerosis, myocardial infarction, hypertension, hypotension, and thrombosis
As the residues in the binding domain do not lie in the disordered region, the binding domain of pregnane X receptor (PXR) protein has a stable structure in protein folding
This study aims to investigate the potent traditional Chinese medicine (TCM) candidates for PXR protein
Summary
Cardiovascular disease, known as loop circulatory system diseases or disorders, is one of the serious diseases including heart disease, stroke, atherosclerosis, myocardial infarction, hypertension, hypotension, and thrombosis. It is the top leading cause of death in the United States and most European countries. More than 83.6 million Americans have the cardiovascular problems; the patients of cardiovascular disease in other Western countries are growing yearly [1]. Obesity, latent diseases, such as diabetes, gout and kidney disease, and bad habits, diet, the environment of toxic substances, and drugs are the risk factors for cardiovascular disease [2,3,4]. Environmental pollution and chemicals promote the occurrence of blood vessel function disorders and cardiovascular diseases. We should consider how to regulate and protect the blood vessels [5]
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