Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators

Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators
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DOI:
10.1016/j.bcp.2006.08.001
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发表时间:
2006-11-15
影响因子:
5.8
通讯作者:
Mossalayi, M. Djavad
Mossalayi, M. Djavad
中科院分区:
医学2区
文献类型:
--
作者:
Mamani-Matsuda, Maria;Kauss, Tina;Mossalayi, M. Djavad

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槲皮素(QU)是植物生物合成的一种常见的黄酮醇,在多种模型中被认为可以调节炎症反应。在本研究中,我们研究了口服或皮下注射QU对慢性大鼠佐剂性关节炎(AA)的体内影响。观察AA诱导后Lewis大鼠的生长延迟和关节炎评分。与未治疗的对照组相比,对关节炎大鼠口服QU (5 × 160 mg/kg)导致临床症状明显减少。皮下注射较低剂量(5 × 60 mg/kg)的QU具有类似的抗关节炎作用,而5 × 30 mg/kg的浓度在这方面无效。最后,在AA诱导前注射相对低剂量的QU (5 × 30 mg/kg)可显著减轻关节炎症状。由于曲被认为可以抑制巨噬细胞来源的细胞因子和一氧化氮(NO),我们随后分析了巨噬细胞的体外反应。在体内和体外,曲霉抗关节炎的作用与腹腔巨噬细胞产生的炎症介质显著减少相关。这些数据表明,QU是一种潜在的针对巨噬细胞炎症反应的抗炎治疗和预防药物。(c) 2006爱思唯尔公司版权所有。
Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants and has been suggested to modulate inflammatory responses in various models. In the present study, we investigated in vivo effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis (AA). Growth delay and arthritic scores were evaluated daily after AA induction in Lewis rats. Oral administration of QU (5 x 160 mg/kg) to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. Intra-cutaneous injections of lower doses (5 x 60 mg/kg) of QU gave similar anti-arthritic effects, while 5 x 30 mg/kg concentrations were inefficient in this respect. Finally, injection of relatively low QU doses (5 x 30 mg/kg) prior to AA induction significantly reduced arthritis signs. As QU was suggested to inhibit macrophage-derived cytokines and nitric oxide (NO), we then analyzed macrophage response ex vivo. Anti-arthritic effects of QU correlated with significant decrease of inflammatory mediators produced by peritoneal macrophages, ex vivo and in vitro. These data indicate that QU is a potential anti-inflammatory therapeutic and preventive agent targeting the inflammatory response of macrophages. (c) 2006 Elsevier Inc. All rights reserved.