Abstract
Purpose: To evaluate the antihypercholesterolemic effect of chemical constituents of W. coagulans by determining inhibitory effect of the compounds against HMG-CoA reductase, using in-silico methods.
 Method: Docking simulations of twenty-one chemical constituents, found in the fruits of W. coagulans were performed against HMGCR(PDB ID: 2Q1L) using Molegro Virtual Docker software. The best docked poses were then selected, based on the docking score and amino acids involved in the interaction within the ligand and active site of protein.
 Results: Five compounds viz. Coagulin D (comp no. 11), Ergosta-5,25-diene-3β,24ε-diol (comp no. 13), Withacoagulin (comp no. 15), and Withaferin (comp no. 16), showed the highest MolDock scores. These compounds with highest docking score, also formed hydrogen bond interactions with His (752), Lys (692, 735), Asp (690), Glu (559) within the binding site of HMG-CoA reductase, thus, halting enzyme activity. Whereas, Withanolide D (comp no. 17) with high MolDock score did not show hydrogen bonding interactions.
 Conclusion: The high MolDock score and maximum binding with catalytic region of the enzyme indicate that compounds selected from the fruits of W. coagulans are potential blockers of HMG-CoA reductase. Thus, the compounds may be useful for the management of hypercholesterolemia, which untreated, often leads to coronary artery disease.
 Keywords: Withania coagulans, Coronary artery disease, HMG-CoA reductase, Molegro virtual docker, Hypercholesterolemia, In silico studies
Highlights
High blood cholesterol level is one of the key factor for progression of Coronary artery disease (CAD) one of the key factors [1]
Many nonclinical and human trials have proved that the risk of coronary complications could be minimized by halting the function of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), a major cholesterol biosynthesis enzyme [2]
Hypercholesterolemia can be treated with statins and other known drugs by inhibiting HMGCR activity [3]
Summary
High blood cholesterol level is one of the key factor for progression of Coronary artery disease (CAD) one of the key factors [1]. Many nonclinical and human trials have proved that the risk of coronary complications could be minimized by halting the function of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), a major cholesterol biosynthesis enzyme [2]. Hypercholesterolemia can be treated with statins and other known drugs (niacins, fibrates etc) by inhibiting HMGCR activity [3]. These commercially available drugs have many adverse signs like hyperuricemia, nausea, diarrhea, gastric irritation, myositis, and abnormal liver function [4]. Researchers have diverted their attention towards medicinal plants to explore the phytochemicals with HMGCR inhibiting activities that could be used to design a new hypolipidemic drug with minimum or no side effects. With the advancement in technology, computational methods have been widely used in evaluating the therapeutic potential of medicinal plants, by determining their activity against the target protein along with their possible mechanism of action
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