Anti-arthritic activity of ferulic acid in complete Freund's adjuvant (CFA)-induced arthritis in rats: JAK2 inhibition
| Autor: | Lijuan Zhu, Yanlin Wei, Nannan Xia, Jiashu Huang, Zhijuan Ren, Feilong Meng, Zhenshan Zhang, Weifeng Zhang, Lei Yang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Coumaric Acids Immunology Freund's Adjuvant Anti-Inflammatory Agents Arthritis Pharmacology Proinflammatory cytokine Ferulic acid Arthritis Rheumatoid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Janus Kinase Inhibitors Pharmacology (medical) Rats Wistar IC50 Janus kinase 2 biology Dose-Response Relationship Drug JAK-STAT signaling pathway Janus Kinase 2 medicine.disease Arthritis Experimental Rats Molecular Docking Simulation 030104 developmental biology chemistry Rheumatoid arthritis Antirheumatic Agents biology.protein Cytokines Tumor necrosis factor alpha Female 030217 neurology & neurosurgery |
| Zdroj: | Inflammopharmacology. 28(2) |
| ISSN: | 1568-5608 |
| Popis: | Ferulic acid (FA), a hydroxycinnamic acid, is an organic compound found in several plant species. Previous studies have shown that FA contains anti-inflammatory and anti-arthritic properties. This study aimed to investigate the anti-arthritic activity and possible mechanism(s) of action of FA in complete Freund’s adjuvant (CFA)-induced arthritis. The progression of rheumatoid arthritis (RA) involves the activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway by proinflammatory cytokines. Molecular docking of FA showed promising Janus kinase 2 (JAK2) inhibition with a docking score of − 6.7, which is comparable with that of ruxolitinib, a standard inhibitor. However, in vitro JAK2 inhibition assay showed a half maximal inhibitory concentration (IC50) of 6.67 ± 0.88 µg/ml. Both doses of FA (25 and 50 mg/kg) significantly attenuated primary (volume of paw edema) and secondary lesions. CFA-induced arthritic rats showed a significant decrease in body weight, A/G ratio, and Hb but showed a greater arthritic index, ESR levels, and percentage of lymphocytes. These alterations were significantly reduced in rats treated with FA and prednisolone. FA also reversed changes to biochemical parameters and inflammatory markers, such as C-reactive protein (CRP) and rhematoid factor (RF). Additionally, we found CFA-induced arthritis triggered the secretion of TNF- α, increased JAK2 levels, and reduced TGF-β levels in tissue homogenates. However, in rats treated with FA, such alterations significantly improved. Thus, our results reveal that FA contains anti-arthritic activity, which is possibly mediated by the inhibition of the JAK/STAT pathway. |
| Databáze: | OpenAIRE |
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