Eco-Innovative Drug Discovery from Shallot (Allium cepa L. var. aggregatum) Peel Waste: Green Extraction Coupled Metabolomic, Transcriptomic, and In Silico Approaches to Inhibit Platelet Aggregation

Arterial thrombosis triggered by thromboxane A₂ mediated platelet activation remains leading in coronary heart disease and ischemic stroke (IS). Since existing antiplatelet agents are limited by resistance and adverse effects, there is a critical need for safer and selective COX inhibitors. Addressing the urgencies to obtain good health and well-being, this study explores the polyphenol-rich peel of Allium cepa L. var. aggregatum (shallot) an agro-industrial by-product as a sustainable source of natural antithrombotic compounds by integrating metabolomics and in silico approach. Temperature-optimized ultrasonic extraction produced distinct metabolite profiles, with LC-HRMS/MS showing the highest metabolite diversity at ۴۰ °C, dominated by quercetin glycosides, isorhamnetin derivatives, and steroidal saponins. Integration of these metabolomic signatures with IS transcriptomic datasets and related databases revealed merging with gene networks pharmacology involved in platelet activation, arachidonic acid (AA) metabolism, and inflammatory signaling, suggesting multi-target activity within thrombo-inflammatory pathways. Molecular docking identified ۲-monolinolein, quercetin diglucoside, bistortaside, schininallylol, and (±)-medicarpin as strong COX-۱ ligands surpassing the affinities of aspirin and flurbiprofen through conserved interactions with Ser۵۳۰ and Tyr۳۸۵. The molecular dynamics (MD) simulation confirmed the stability of polyphenolic ligands, while lipidic constituents displayed distinct hinge-like motions. Additionally, MM-GBSA analysis produced the favorable binding energies of ۲-monolinolein and quercetin glycosides, providing the first evidence that shallot peel contains metabolites capable of forming highly stable COX-۱ complexes. Collectively, these findings establish shallot peel as a mechanistically supported and sustainable source of natural COX-۱ modulators with promising eco-innovative antithrombotic potential.

کلیدواژه ها:

Allium cepa L. var. aggregatum ، Green extraction ، ischemic stroke ، Good Health and Well-being ، Transcriptomic ، Anti-platelet