Quercetin attenuates zymosan-induced arthritis in mice

Quercetin attenuates zymosan-induced arthritis in mice
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DOI:
10.1016/j.biopha.2018.03.057
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发表时间:
2018-06-01
影响因子:
7.5
通讯作者:
Verri, Waldiceu A., Jr.
Verri, Waldiceu A., Jr.
中科院分区:
医学2区
文献类型:
--
作者:
Guazelli, Carla F. S.;Staurengo-Ferrari, Larissa;Verri, Waldiceu A., Jr.

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类风湿性关节炎(RA)是一种慢性自身免疫性疾病,其特征是关节病变、炎症细胞募集和促炎细胞因子水平升高。酵母聚糖的关节内给药是一种促进类似RA的炎症参数的实验模型。因此,该模型用于研究槲皮素治疗关节炎症的功效。槲皮素剂量依赖性地减少酵母多糖诱导的痛觉过敏、关节水肿和中性粒细胞向膝关节腔的募集。组织学分析证实,槲皮素抑制酵母多糖诱导的关节炎。槲皮素治疗还抑制酵母多糖诱导的还原型谷胱甘肽(GSH)水平、TNF α和IL-1 β产生以及gp 91(phox)、前内皮素原-1(preproET-1)和环氧合酶-2 mRNA表达的耗竭。槲皮素的这些分子作用与抑制核因子kappaB和诱导核因子红细胞2相关因子(Nrf 2)/家庭加氧酶(HO-1)通路有关。因此,槲皮素在实验性关节炎中具有抗炎、镇痛和抗氧化作用,表明槲皮素是治疗关节炎的可能候选物。
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular lesions, recruitment of inflammatory cells and increased levels of pro-inflammatory cytokine. The intra-articular administration of zymosan is an experimental model that promotes inflammatory parameters resembling RA. Therefore, this model was used to investigate the efficacy of quercetin as a treatment of articular inflammation. Treatment with quercetin dose-dependently reduced zymosan-induced hyperalgesia, articular edema and the recruitment of neutrophils to the knee joint cavity. Histological analysis confirmed that quercetin inhibited zymosan-induced arthritis. The treatment with quercetin also inhibited zymosan-induced depletion of reduced glutathione (GSH) levels, TNF alpha and IL-1 beta production, and gp91(phox), prepro-endothelin-1 (preproET-1), and cyclooxygenase-2 mRNA expression. These molecular effects of quercetin were related to the inhibition of the nuclear factor kappaB and induction of Nuclear factor erythroid 2-related factor (Nrf2)/home oxygenase (HO-1) pathway. Thus, quercetin exerted anti-inflammatory, analgesic and antioxidant effects in experimental arthritis, suggesting quercetin is a possible candidate for arthritis treatment.