Abstract

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.

Graphic abstract

中文翻译：

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阿魏酸在完全弗氏佐剂（CFA）诱导的大鼠关节炎中的抗关节炎活性：JAK2抑制。

摘要

阿魏酸（FA）是一种羟基肉桂酸，是几种植物中发现的一种有机化合物。先前的研究表明，FA具有抗炎和抗关节炎特性。这项研究旨在调查完全弗氏佐剂（CFA）诱导的关节炎中FA的抗关节炎活性和可能的​​作用机制。类风湿关节炎（RA）的进展涉及促炎性细胞因子激活Janus激酶信号转导子和转录激活子（JAK / STAT）途径。FA的分子对接显示出有希望的Janus激酶2（JAK2）抑制作用，对接得分为-6.7，与标准抑制剂ruxolitinib相当。但是，体外JAK2抑制试验显示最大抑制浓度（IC50）为6.67±0.88 µg / ml。两种剂量的FA（25和50 mg / kg）均显着减轻了原发性（足部水肿的体积）和继发性病变。CFA诱发的关节炎大鼠的体重，A / G比和Hb明显降低，但关节炎指数，ESR水平和淋巴细胞百分比却更高。在用FA和泼尼松龙治疗的大鼠中，这些改变明显减少。FA还逆转了生化参数和炎症标志物（例如C反应蛋白（CRP）和类风湿因子（RF））的变化。此外，我们发现CFA诱发的关节炎触发了组织匀浆中TNF-α的分泌，JAK2水平升高和TGF-β水平降低。然而，在用FA治疗的大鼠中，这种改变显着改善。因此，我们的结果表明FA含有抗关节炎活性，

图形摘要