In Silico Study of Potential Anti-Cholesterol of Garlic (Allium sativum L.) Against the HMG-CoA Reductase Enzyme

Abstract

Dyslipidemia is a major risk factor for cardiovascular diseases, characterized by elevated total cholesterol and LDL levels. Statins, as first-line therapy, have certain limitations, highlighting the need for safer alternative candidates. Garlic (Allium sativum L.) contains various bioactive compounds with potential cholesterol-lowering activity. This study aimed to evaluate the potential of garlic active compounds as inhibitors of HMG-CoA reductase using an in silico approach. The methods included Lipinski’s Rule of Five analysis, ADME-Tox prediction, pharmacophore modeling, and molecular docking using AutoDock against the HMG-CoA reductase receptor (PDB ID: 3CCW), with simvastatin as a positive control. The results showed that all tested compounds met the drug-likeness criteria. ADME-Tox prediction indicated favorable absorption and distribution profiles for most compounds, although potential mutagenicity was observed. Pharmacophore modeling and molecular docking results revealed that tryptophan exhibited the best binding affinity with a binding energy of −6.39 kcal/mol and an inhibition constant of 20.68 μM, along with amino acid interactions similar to simvastatin. Therefore, tryptophan has potential as a cholesterol-lowering drug candidate, although further studies are required to address its safety profile.