Dual Therapeutic Potential of Novel Cornallegic Acid: <i>In Vitro</i> Anti-inflammatory and ROS Suppression with Computational Insights from Docking, ADMET and DFT Studies

Inflammation is a key mechanism in chronic and autoimmune disorders, creating an urgent need for effective therapies. Cornus macrophylla, traditionally used in medicine, has recently gained attention for its anti- inflammatory properties. This study aimed to isolate and evaluate bioactive compounds from C. macrophylla bark, focusing on cornallegic acid and its anti-inflammatory potential. Cornallegic acid was assessed using experimental and computational approaches. Its lipoxygenase (LOX) inhibitory activity was tested in vitro and in silico. Reactive oxygen species (ROS) suppression was evaluated in a respiratory burst assay with human neutrophils. Cornallegic acid exhibited strong anti-inflammatory activity, inhibiting LOX with an IC[Formula: see text] of 78.1 ± 0.03 [Formula: see text]M. Molecular docking revealed a binding affinity of –6.481 kcal/mol with 15-LOX, showing interactions with catalytic residues His513 and His518. In human neutrophils, it suppressed ROS production with an IC[Formula: see text] of 298.21 ± 0.037 [Formula: see text]M, comparable to indomethacin (IC 50 = 271.14 ± 0.032 [Formula: see text]M). ADMET profiling and DFT analysis further supported its therapeutic potential, highlighting dual mechanisms of LOX inhibition and ROS modulation. Cornallegic acid is a promising natural anti-inflammatory agent with dual activity, making it a potential candidate for managing inflammatory and autoimmune conditions. This discovery emphasizes C. macrophylla relevance in modern pharmacology, offering a novel avenue for drug development.