Molecular docking analysis of Citrus aurantifolia peel bioactive compounds against fshr, androgen receptor, and PCSK4 in hyperlipidemia-associated male reproductive dysfunction
TL;DR
The selected C. aurantifolia peel compounds showed predicted interactions with the three target proteins; however, molecular docking alone does not establish nutraceutical efficacy, bioavailability, safety, receptor activation, or clinical benefit, however, further experimental validation is required.
Abstract
Hyperlipidemia is a diet-induced metabolic disorder that adversely affects systemic metabolism and reproductive function in males. Plant-derived bioactive compounds possess antioxidant, hypolipidemic, and metabolic regulatory activities. This study aimed to investigate the predicted interactions of bioactive compounds from C. aurantifolia peel with proteins involved in metabolic and reproductive pathways using an in silico molecular-docking approach. This in silico molecular docking study was conducted from January to April 2026 at the National Research and Innovation Agency in Indonesia. Ten bioactive compounds identified by GC–MS analysis of Citrus aurantifolia peel ethanol extract were used as test ligands FSHR (PDB ID: 2AM9), androgen receptor (PDB ID: 1XWD), and PCSK4 (UniProt ID: Q6UW60) were prepared using BIOVIA Discovery Studio 2021. Molecular docking was performed using AutoDock Vina in PyRx, with simvastatin as the reference ligand. The docking results were evaluated using the predicted binding affinities and interaction profiles. Pterin-6- carboxylic acid showed the most favorable predicted docking score for FSHR (−7.2 kcal/mol), whereas m-toluic acid showed the most favorable predicted docking scores for the androgen receptor and PCSK4 (−7.5 and −7.8 kcal/mol, respectively). In conclusion, the selected C. aurantifolia peel compounds showed predicted interactions with the three target proteins; however, molecular docking alone does not establish nutraceutical efficacy, bioavailability, safety, receptor activation, or clinical benefit. However, further experimental validation is required.