In silico molecular docking study of flavanols methyl ethers from Alpinia monopleura as potential inhibitors of inflammatory targets

Introduction: Inflammation plays a central role in various chronic diseases. Flavonoids are widely recognized for their pharmacological potential, including anti-inflammatory properties. This study aimed to isolate O-methylated flavonols from Alpinia monopleura and to predict their potential anti-inflammatory activity using computational approaches. Methods: Rhizomes of A. monopleura were extracted with methanol, partitioned, and fractionated by vacuum liquid chromatography (VLC). Isolated compounds were characterized by 1H- and 13C-NMR spectroscopy. The anti-inflammatory potential was evaluated by molecular docking against multiple inflammation-related targets using AutoDock Vina, with native ligands as references, followed by in silico pharmacokinetic and toxicity predictions using pkCSM and ProTox 3.0. Results: Two O-methylated flavonols, kaempferol 3,7,4′-trimethyl ether (2a) and quercetin 3,7,4′-trimethyl ether (2b), were isolated from the ethyl acetate fraction of A. monopleura. Both compounds exhibited favorable binding energies toward multiple inflammatory targets. Compounds 2a and 2b showed stronger binding than native ligands against inducible nitric oxide synthase (iNOS), lipoxygenase (LOX), and mPGES-1, and interacted with COX-2, IKK, JAK2, and NOX5, which are key proteins regulating inflammatory signaling pathways, with binding energies generally below −8.0 kcal/mol. Predicted pharmacokinetic profiles indicated good intestinal absorption and membrane permeability, with acceptable toxicity, with binding energies generally below −8.0 kcal/mol. Predicted pharmacokinetic profiles indicated good intestinal absorption and membrane permeability, with acceptable toxicity. Conclusion: O-methylated flavonols from A. monopleura showed potential as multi-target anti-inflammatory leads based on in silico analyses. These findings provide a scientific basis for further experimental studies and support the exploration of A. monopleura–derived flavonols as candidate compounds for the development of safer anti-inflammatory agents. Future in vitro and in vivo studies are warranted to validate their pharmacological efficacy and relevance to clinical practice.