Therapeutic effects of <i>Chrysanthemum zawadzkii</i> and its active compound eupatilin in rheumatoid arthritis: <i>in silico</i> and <i>in vitro</i> validation

The 50% ethanol extract of the aerial parts of <i>Chrysanthemum zawadzkii</i> (CZ extract) was evaluated for its inhibitory effects on the production of NO, TNF-α, and XO, and seven isolated flavonoids were tested for COX-2 inhibitory activity. The ethanol extract of <i>C. zawadzkii</i> exhibited a strong inhibitory effect on NO and XO overproduction, with IC₅₀ values of 6.91 µg/mL and 83.48 µg/mL, respectively. Eupatilin (<b>3</b>) significantly suppressed COX-2 expression at a concentration of 100 µM (<i>p</i> < 0.05). Molecular docking analysis and ADMET predictions revealed that eupatilin forms hydrogen bonds and π-σ interactions, which significantly contribute to its binding affinity with residues in the enzyme's active site. Additionally, it exhibits low oral toxicity and good bioavailability in humans. These findings demonstrate the potential of CZ extract and its active compound, eupatilin, as naturally occurring agents with anti-heumatoid arthritis activities, capable of potently inhibiting COX-2 signalling <i>in vitro.</i>