<i>Fraxinus excelsior</i> L. Hydromethanolic Extract Modulates Rheumatoid Arthritis Induced by Complete Freund’s Adjuvant in Rats Emphasizing Inflammatory and Antioxidant Pathways
| Author | Shirin Asar | en |
| Author | Mohammad Mehdi Gravandi | en |
| Author | Hosna Khazaei | en |
| Author | Sajad Fakhri | en |
| Author | Amin Iranpanah | en |
| Author | Ehsan Mohammadi-Noori | en |
| Author | Khodabakhsh Rashidi | en |
| Author | Ina Yosifova Aneva | en |
| Author | Maryam Naseri | en |
| Author | Mohammad Hosein Farzaei | en |
| Orcid | Mohammad Mehdi Gravandi [0000-0002-7995-5285] | en |
| Orcid | Hosna Khazaei [0000-0002-1058-7613] | en |
| Orcid | Sajad Fakhri [0000-0001-8265-8284] | en |
| Orcid | Khodabakhsh Rashidi [0000-0002-8144-074X] | en |
| Orcid | Mohammad Hosein Farzaei [0000-0001-7081-6521] | en |
| Issued Date | 2025-05-31 | en |
| Abstract | 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. | en |
| DOI | https://doi.org/10.5812/jjnpp-160639 | en |
| Keyword | Rheumatoid Arthritis | en |
| Keyword | <i>Fraxinus excelsior </i>L. | en |
| Keyword | Inflammation | en |
| Keyword | Antioxidant | en |
| Publisher | Brieflands | en |
| Title | <i>Fraxinus excelsior</i> L. Hydromethanolic Extract Modulates Rheumatoid Arthritis Induced by Complete Freund’s Adjuvant in Rats Emphasizing Inflammatory and Antioxidant Pathways | en |
| Type | Research Article | en |