title: Treatment of cardiovascular disease by traditional Chinese medicine against pregnane X receptor.
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.
authors: School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan.
authors: Kuen-Bao
authors: KB
authors: Chen
authors: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors: Hsin-Yi
authors: HY
authors: Chen
authors: School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors: Kuan-Chung
authors: 0000-0003-0223-1577
authors: KC
authors: Chen
authors: School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan ; Human Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors: Calvin Yu-Chian
authors: 0000-0003-3306-250X
authors: CY
authors: Chen
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D016014:Linear Models; D008516:Medicine, Chinese Traditional; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D000077297:Pregnane X Receptor; D017433:Protein Structure, Secondary; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D060388:Support Vector Machine; D013816:Thermodynamics
chemical_list: D004365:Drugs, Chinese Herbal; D064267:Intrinsically Disordered Proteins; D008024:Ligands; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid