Studi In Silico Potensi Senyawa Aktif Daun Rambusa (Passiflora Foetida L.) Sebagai Antikolesterol

Abstract

Hypercholesterolemia is a major risk factor for cardiovascular diseases, associated with elevated blood cholesterol levels. The enzyme HMG-CoA reductase plays a crucial role in cholesterol biosynthesis and serves as a primary target for lipid-lowering therapy. Statins, such as simvastatin, are widely used to inhibit this enzyme; however, their long-term use may lead to adverse effects. Therefore, the exploration of natural compounds with potential antihypercholesterolemic activity is highly needed. Rambusa leaves (Passiflora foetida L.) are known to contain various secondary metabolites, particularly flavonoids, which are predicted to act as HMG-CoA reductase inhibitors. This study aimed to evaluate the potential of flavonoid compounds from rambusa leaves as antihypercholesterolemic agents using an in silico approach. The methodology included compound screening based on Lipinski’s Rule of Five, ligand and receptor preparation, docking validation, and molecular docking analysis using AutoDockTools and PyRx. The target protein structure of HMG-CoA reductase was obtained from the Protein Data Bank (PDB ID: 3CCW), with simvastatin used as a positive control. The results showed that out of 12 identified flavonoid compounds, five met Lipinski’s criteria and were further analyzed. All tested ligands exhibited negative binding energy values against HMG-CoA reductase. Luteolin demonstrated the best binding affinity with a binding energy of −5.62 kcal/mol and an inhibition constant of 76.52 µM, followed by 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one and naringenin. Molecular interaction analysis revealed hydrogen bonding and hydrophobic interactions with key amino acid residues at the enzyme’s active site. In conclusion, flavonoids from Passiflora foetida L. show promising potential as HMG-CoA reductase inhibitors and may serve as candidates for natural antihypercholesterolemic drug development.