fraxinus excelsior l. hydromethanolic extract modulates rheumatoid arthritis induced by complete freund’s adjuvant in rats emphasizing inflammatory and antioxidant pathways

Background: rheumatoid arthritis (ra) is a persistent inflammatory condition characterized by an imbalance in oxidative stress and chronic inflammation of joint tissues. objectives:fraxinus excelsior l., commonly known as ash, has demonstrated anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties. the present study aims to evaluate the therapeutic effects of f. excelsior l. bark hydromethanolic extract (fee) in the management of ra. methods: thirty male rats were randomly divided into six groups: normal control, ra, three dosages of fee (20, 40, 80 mg/kg/day, orally), and prednisolone (10 mg/kg/day, orally). these doses were selected to evaluate the potential dose-dependent effects of fee. the hot plate test, serum glutathione (gsh), malondialdehyde (mda), and histopathological investigations were assessed. the activity of matrix metalloproteinases (mmp-2 and mmp-9) was measured using zymography. liquid chromatography-tandem mass spectrometry (lc-ms/ms) analysis previously confirmed the presence of coumarins in fee. results: the fee significantly reduced pain perception in the hot plate test (p < 0.001). malondialdehyde levels were significantly elevated in ra rats (p < 0.001) but were reduced following fee and prednisolone treatment (p < 0.01). similarly, gsh levels were significantly decreased in ra rats (p < 0.001) but were restored in fee-treated groups (p < 0.01, p < 0.001 for higher doses). the fee also significantly decreased mmp-2 and mmp-9 activity (p < 0.001), confirming its anti-inflammatory potential. histopathological analyses corroborated these findings, demonstrating reduced synovial hyperplasia and inflammatory cell infiltration in fee-treated groups. coumarins in fee are known to modulate inflammation through inhibition of mmp-2 and mmp-9 activity and regulate oxidative stress by enhancing antioxidant defenses, including increasing gsh levels and reducing mda accumulation. conclusions: given the improvements in behavioral, biochemical, and histopathological parameters alongside modulation of inflammation (mmp-2, mmp-9) and oxidative stress (mda, gsh), our results suggest that fee, rich in coumarins, could be a promising candidate for ra management.