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在关节炎大鼠模型中,牡荆素通过调节JAK/STAT/SOCS信号通路减轻炎症并增强细胞凋亡。

Vitexin alleviates inflammation and enhances apoptosis through the regulation of the JAK/STAT/SOCS signaling pathway in the arthritis rat model.

作者信息

Zhang Daojian, Ning Taiguo, Wang Hongbin

机构信息

Department of Orthopedics, Peking University First Hospital, Beijing, China.

出版信息

J Biochem Mol Toxicol. 2022 Dec;36(12):e23201. doi: 10.1002/jbt.23201. Epub 2022 Aug 27.

DOI:10.1002/jbt.23201
PMID:36029189
Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder. RA is progressive and needs long-term treatment. Vitexin is a naturally-occurring flavonoid that is identified in various plant sources. Vitexin is demonstrated to produce antioxidant effects with numerous pharmacological activities. This experimental in vivo study assessed the antiarthritic and apoptotic role of a natural plant extract, vitexin, on RA. Collagen-induced arthritis (CIA) rat model Sprague Dawley males were grouped into five sets with six rats each: control, CIA, CIA + vitexin (10 mg/kg bw), CIA + Methotrexate (1 mg/kg bw), and vitexin (10 mg/kg bw) alone. The body weight, organ weight, biochemical assay, inflammatory enzymes, apoptosis, and cytokines levels were evaluated and compared among groups. Janus kinase (JAK)/signal transducer and activator of transcription (STAT)/suppressors of cytokine signaling (SOCS) levels and histopathology of ankle joints were also studied and compared. Significance was considered at a p < 0.05. Vitexin (10 mg/kg bw) significantly reduced the inflammatory enzyme markers, interleukin (IL)-1β, IL-6, IL-17, IL-4, IL-10, tumor necrosis factor-α, interferon-γ, and iNOS levels in arthritis rats (p < 0.05). Vitexin significantly improved collagen-induced arthritic histological changes (p < 0.05). Vitexin also reduced JAK/STAT expressions associated with inflammation and significantly increased elevated SOCS levels (p < 0.05). Aberration in apoptosis, inflammatory mediators, C-reactive protein, and rheumatoid factor levels in the arthritic rats reverted to normal with vitexin. These results emphasize that vitexin possesses anti-inflammatory and apoptotic activity via the regulation of JAK/STAT/SOCS signaling in CIA in a rat model. Hence, vitexin is a promising auxiliary drug for RA treatment.

摘要

类风湿性关节炎(RA)是一种慢性炎症性自身免疫性疾病。RA具有进行性,需要长期治疗。牡荆素是一种天然存在的黄酮类化合物,存在于多种植物来源中。已证明牡荆素具有抗氧化作用及多种药理活性。这项体内实验研究评估了天然植物提取物牡荆素对RA的抗关节炎和凋亡作用。将胶原诱导性关节炎(CIA)大鼠模型的雄性Sprague Dawley大鼠分为五组,每组六只:对照组、CIA组、CIA + 牡荆素(10 mg/kg体重)组、CIA + 甲氨蝶呤(1 mg/kg体重)组和单独使用牡荆素(10 mg/kg体重)组。评估并比较了各组的体重、器官重量、生化检测、炎症酶、细胞凋亡和细胞因子水平。还研究并比较了Janus激酶(JAK)/信号转导和转录激活因子(STAT)/细胞因子信号转导抑制因子(SOCS)水平以及踝关节的组织病理学。p < 0.05被视为具有统计学意义。牡荆素(10 mg/kg体重)显著降低了关节炎大鼠体内的炎症酶标志物、白细胞介素(IL)-1β、IL-6、IL-17、IL-4、IL-10、肿瘤坏死因子-α、干扰素-γ和诱导型一氧化氮合酶水平(p < 0.05)。牡荆素显著改善了胶原诱导性关节炎的组织学变化(p < 0.05)。牡荆素还降低了与炎症相关的JAK/STAT表达,并显著提高了升高的SOCS水平(p < 0.05)。牡荆素使关节炎大鼠的细胞凋亡、炎症介质、C反应蛋白和类风湿因子水平的异常恢复正常。这些结果强调,牡荆素在大鼠模型的CIA中通过调节JAK/STAT/SOCS信号传导具有抗炎和凋亡活性。因此,牡荆素是一种有前景的RA治疗辅助药物。

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