Abstract
Inflammation is an important immune response in our organism, the intervention of anti-inflammatory substances is critical to control inflammation, in which Cyclooxygenase-2 (COX-2) serves as a key target to inhibit inflammatory factors. This study employed ultrasonic-assisted extraction (UAE) to prepare isoorientin from corn silk (Zea mays L.), optimizing extraction parameters to achieve a maximum yield of 1.26 mg/g isoorientin under optimal conditions. A quantitative structure-activity relationship (QSAR) model was utilized to screen four potential COX-2 inhibitors, including isoorientin, whose excellent inhibitory activities were validated through in vitro COX-2 inhibition assays. Notably, isoorientin demonstrated significant COX-2 inhibitory potency with an IC(50) value of 18.38 ± 0.38 μg/mL. Oral toxicity testing revealed that isoorientin exhibited non-toxic or low-toxic characteristics compared to the other three compounds, indicating superior safety profiles. Molecular docking and molecular dynamics (MD) simulations were combined to elucidate the binding mechanism of isoorientin with COX-2, confirming that stable interactions were mediated by hydrogen bonding and hydrophobic effects. This work provides a theoretical framework for the rapid screening of COX-2 inhibitory compounds, establishes a high-value utilization pathway for corn silk, thereby contributing to the advancement of green and sustainable development.