Phytochemical Characterization and Antipyretic and Antinociceptive Activities of Echinops orientalis Trautv. Methanolic Flower Extract: Evidence from In vivo Studies, Network Pharmacology and Molecular Docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinops L. (Asteraceae), known as globe thistles (Shakroka in Kurdish), is traditionally used to treat fever and pain. AIM OF THE STUDY: To characterize the phytochemical profile of the methanolic flower extract (MFE) of Echinops orientalis Trautv., and evaluate its antipyretic and antinociceptive activities in vivo, supported by network pharmacology and molecular docking. MATERIALS AND METHODS: Phytochemical constituents were characterized using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Antipyretic and antinociceptive activities were evaluated using brewer's yeast-induced pyrexia, acetic acid-induced writhing and formalin-induced licking models in rats. Potential molecular mechanisms were investigated through network pharmacology and molecular docking analyses. RESULTS: HPLC quantified ten phenolics/flavonoids (chlorogenic acid most abundant, 605 ppm) and four thiophenes; GC-MS identified three fatty acids and one fatty acid derivative dominated by n-pentadecanoic acid (57.97%). MFE significantly attenuated pyrexia with maximum effect at dose 200mg/kg (p<0.05), reduced writhing significantly at all doses, and significantly decreased licking time in the late phase. Network pharmacology of seventeen of the eighteen identified constituents predicted 428 targets shared with fever- and pain-associated genes, with SRC, EGFR, AKT1, STAT3 and IL6 as top hubs by degree centrality. Docking showed the strongest predicted binding for apigenin-TBXAS1 (-8.66 kcal/mol) and quercetin-SRC (-7.96 kcal/mol). These in silico findings were not experimentally verified. CONCLUSIONS: Echinops orientalis MFE shows antipyretic and antinociceptive potential, supporting its traditional use. Computational predictions suggest modulation of cyclooxygenase (COX-2), prostaglandin E2 receptor (EP2), thromboxane synthase (TBXAS1) and interconnected inflammatory pathways, a hypothesis requiring experimental validation and further preclinical investigation.