Evaluation of hypolipidemic potentials of phytoconstituents in Cymbopogon citratus and Piper guineense: A Computational Approach

Abstract

Background: Hyperlipidemia causes atherosclerotic cardiovascular disease which constitutes one of the most common cardiovascular risk factors globally. The adverse effects and cost-effectiveness of hypolipidemic drugs as well as safety on the use of herbs remain a major challenge. Consequently, the hypolipidemic potentials and toxicity profile of phytoconstituents in Cymbopogon citratus and Piper guineense were evaluated using computation approach.  

 Methods: Molecular docking was carried out using Maestro 12.8, while SwissADME and ProTox-II were used to establish the drug-likeness and toxicity profile of the phytoconstituents. The chemical structures of the phytoconstituents were docked against four key protein targets implicated in hyperlipidemia. The protein targets were 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase (HMG-CoA Reductase, PDB ID 1HWK), Peroxisome Proliferator-Activated Receptor Gamma (PPAR-?, PDB ID 6ENQ), Niemann-Pick C1-Like 1 (NCP1L1, PDB ID 7WGN) and Hydroxycarboxylic Acid Receptor 2 (HM7A4, PDB ID 8K5B). Atorvastatin, lanifibranor, Ezetimibe and niacin were used as standards.

 Results: The in silico analysis of both plants identified some compounds with binding energies in the range of -7.00  to -8.76 kcal/mol. Pyridine-3-carboxylic acid with binding energy -8.76 kcal/mol from cymbopogon citratus possesses the greatest binding affinity, while the next was 7-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylhepta-2,4,6-trien-1-one (piperettine) with binding energy -8.57 kcal/mol from Piper guineense. (1S,2S,4aR,8aR)-2-(1,3-benzodioxol-5-yl)-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-piperidin-1-ylmethanone) with binding affinity of 7.51 kcal/mol NCP1L1 (7WGN)  appears to be an outstanding ligand for drug.

 Conclusion: The findings suggest that both plants contain compounds with hypolipidemic activity which justifies their traditional use in treatment of hyperlipidemia. However, lead optimization and a wet experiment will be required to validate the outcome of this study.