From herb to headache relief: A network-based study on Origanum vulgare L

• Oregano compounds showed strong multi-target potential against migraine pathways. • Luteolin, apigenin, and rosmarinic acid exhibited high docking affinities. • Essential oil terpenoids showed broad interactions with migraine-related targets. • Network pharmacology revealed key nodes regulating neurovascular migraine mechanisms. • Results support Origanum vulgare as a promising complementary migraine therapy. Migraine is a complex neurological disorder characterized by recurrent headaches influenced by genetic, hormonal, vascular, and neuroinflammatory factors. Key proteins such as NOS3, DRD2, ESR1, HTR2A, CACNA1A, TRPV1, and CALCA regulate vascular tone, neurotransmission, hormonal balance, and pain signaling. Origanum vulgare L. (oregano), recognized in modern Chinese medicine as Niu Zhi (牛至), is recorded as Herba Origani Vulgaris and has documented traditional indications including heat-clearing, dampness-draining, and treatment of fever/heat-stroke–type conditions. Modern pharmacological evidence further supports anti-inflammatory, antioxidant, analgesic, and neuroprotective activities, largely attributed to phenolic monoterpenes (e.g., carvacrol, thymol) and polyphenols (e.g., rosmarinic acid, flavonoids). However, its molecular mechanisms in migraine-related neurovascular and neuroinflammatory pathways remain insufficiently characterized . This study investigated the therapeutic potential of oregano-derived bioactive compounds against migraine using an integrative in silico approach combining network pharmacology and molecular docking. Phytochemical data were obtained from PubChem, and migraine-associated targets from UniProt and DisGeNET. Compound–target interactions were predicted using BindingDB, SwissTargetPrediction, SEA, and TargetNet. Gene and protein interaction networks were constructed with GeneMANIA and STRING, while molecular docking via AutoDock Vina assessed binding affinities between compounds and key proteins. Luteolin, apigenin, and rosmarinic acid emerged as top-performing compounds, showing strong and consistent affinities across multiple targets. These compounds effectively modulated nitric oxide pathways and dopaminergic and serotonergic systems central to migraine pathophysiology. Network analyses highlighted target hubs related to neurovascular and hormonal regulation. The findings provide computational evidence supporting Origanum vulgare as a promising multi-target candidate for complementary migraine therapy and offer mechanistic insights into its pharmacological effects, forming a foundation for further experimental validation and development of oregano-based therapeutic strategies.