Fattori Victor, Pinho-Ribeiro Felipe A, Borghi Sergio M, Alves-Filho José C, Cunha Thiago M, Cunha Fernando Q, Casagrande Rubia, Verri Waldiceu A
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86057-970, Londrina, Paraná, Cx Postal 10.011, Brasil.
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brasil.
Inflamm Res. 2015 Dec;64(12):993-1003. doi: 10.1007/s00011-015-0885-y. Epub 2015 Oct 11.
This study aimed at evaluating the activity of curcumin in superoxide anion-induced pain-like behavior and leukocyte recruitment in mice.
Administration of curcumin 10 mg/kg subcutaneously 1 h before stimulus.
KO2 was used as superoxide anion donor. Overt pain-like behaviors were determined by the number of abdominal writhings, paw flinches and time spent licking the paw. Mechanical and thermal hyperalgesia were determined using an electronic anesthesiometer and hot plate, respectively. Cytokine concentration and NF-κB activity were determined by ELISA, antioxidant effect by nitrobluetretrazolium assay and ABTS radical scavenging ability. Myeloperoxidase activity was measured by colorimetric assay. The Nrf2, heme oxygenase-1 (HO-1) and gp91phox mRNA expression was determined by quantitative PCR. Data were analyzed by ANOVA followed by Tukey's post hoc and considered significant when p<0.05.
Curcumin inhibited superoxide anion-induced overt pain-like behaviors as well as mechanical and thermal hyperalgesia. Curcumin also inhibited superoxide anion-induced leukocyte recruitment in the peritoneal cavity and in the paw skin inhibited myeloperoxidase activity, oxidative stress, IL-1β and TNF-α production and NF-κB activation as well as enhanced IL-10 production, and HO-1 and Nrf2 mRNA expression.
Curcumin inhibits superoxide anion-induced inflammatory pain-like behaviors and leukocyte recruitment by targeting inflammatory molecules and oxidative stress; and inducing antioxidant and anti-inflammatory pathways.
本研究旨在评估姜黄素在超氧阴离子诱导的小鼠疼痛样行为和白细胞募集方面的活性。
在刺激前1小时皮下注射10mg/kg姜黄素。
使用超氧钾(KO2)作为超氧阴离子供体。通过腹部扭体次数、爪退缩次数和舔爪时间来确定明显的疼痛样行为。分别使用电子麻醉仪和热板来测定机械性和热痛觉过敏。通过酶联免疫吸附测定(ELISA)来测定细胞因子浓度和核因子κB(NF-κB)活性,通过氮蓝四唑试验和ABTS自由基清除能力来测定抗氧化作用。通过比色法测定髓过氧化物酶活性。通过定量聚合酶链反应(PCR)来测定核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)和gp91phox的信使核糖核酸(mRNA)表达。数据通过方差分析(ANOVA),随后进行Tukey事后检验,当p<0.05时被认为具有显著性。
姜黄素抑制超氧阴离子诱导的明显疼痛样行为以及机械性和热痛觉过敏。姜黄素还抑制超氧阴离子诱导的腹腔内白细胞募集,并且在爪皮肤中抑制髓过氧化物酶活性、氧化应激、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的产生以及NF-κB激活,同时增强IL-10的产生以及HO-1和Nrf2的mRNA表达。
姜黄素通过靶向炎症分子和氧化应激,并诱导抗氧化和抗炎途径,来抑制超氧阴离子诱导的炎症性疼痛样行为和白细胞募集。