Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Functional Foods and Nutraceuticals Unit, Department of Biochemistry, School of Sciences, Federal University of Technology, Akure, Ondo State, Nigeria.
Cell Biochem Funct. 2019 Oct;37(7):474-485. doi: 10.1002/cbf.3413. Epub 2019 Jul 31.
The effect of quercetin was assessed in rats induced with complete Freund adjuvant (CFA). Arthritis scores, paw oedema, latency, activities of myeloperoxidase (MPO), ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), and ectoadenosine deaminase (E-ADA) in lymphocytes were determined. Furthermore, nucleotide and nucleoside levels as well as the secretion of pro- and anti-inflammatory cytokines were evaluated. Animals were treated with saline and quercetin in doses of 5, 25, and 50 mg/kg for 45 days. The result revealed that quercetin (50 mg/kg) reduced arthritis score and paw oedema, and increased the latency in the thermal hyperalgesia test. Histopathological analysis showed that all the doses of quercetin reduced infiltration of inflammatory cells. MPO activity was increased in the arthritis group; however, quercetin reduced this activity. E-NTPDase activity was increased in lymphocytes of arthritis rats, and treatment with quercetin reversed this increase. However, E-ADA activity was reduced in the arthritis group, and treatment with quercetin modulated the activity of this enzyme in arthritis rat groups. Serum adenosine levels were increased in arthritis, and the levels were lowered with quercetin treatment. Quercetin treatment in arthritis groups decreased the elevated levels of cytokines in the arthritis control group. Thus, quercetin demonstrated an anti-inflammatory effect, and this flavonoid may be a promising natural compound for the treatment of arthritis. SIGNIFICANCE OF THE STUDY: Quercetin may represent a potential therapeutic compound in the treatment of rheumatoid arthritis. Findings from this study indicate that quercetin suppresses swelling and attenuates the underlying inflammatory responses. This is the first report where quercetin was shown to modulate the immune response to arthritis via attenuation of the purinergic system (E-NTPDase and E-ADA activities) and the levels of IFN-gamma and IL-4. Thus, this work is relevant to basic research and may be translated into clinical practice.
槲皮素对完全弗氏佐剂（CFA）诱导的大鼠的作用进行了评估。测定关节炎评分、爪肿胀、潜伏期、髓过氧化物酶（MPO）、外核苷酸三磷酸二磷酸水解酶（E-NTPDase）和外腺苷脱氨酶（E-ADA）在淋巴细胞中的活性。此外，还评估了核苷酸和核苷水平以及促炎和抗炎细胞因子的分泌。动物用生理盐水和 5、25 和 50mg/kg 剂量的槲皮素治疗 45 天。结果表明，槲皮素（50mg/kg）降低关节炎评分和爪肿胀，并增加热痛觉过敏试验中的潜伏期。组织病理学分析表明，槲皮素的所有剂量均减少了炎症细胞的浸润。关节炎组 MPO 活性增加；然而，槲皮素降低了这种活性。关节炎大鼠淋巴细胞中 E-NTPDase 活性增加，槲皮素治疗逆转了这种增加。然而，关节炎组 E-ADA 活性降低，槲皮素调节关节炎大鼠组中该酶的活性。关节炎时血清腺苷水平升高，槲皮素治疗降低其水平。关节炎组用槲皮素治疗降低关节炎对照组细胞因子的升高水平。因此，槲皮素表现出抗炎作用，这种类黄酮可能是治疗关节炎的有前途的天然化合物。研究的意义：槲皮素可能代表治疗类风湿性关节炎的潜在治疗化合物。本研究的结果表明，槲皮素抑制肿胀并减轻潜在的炎症反应。这是首次报道槲皮素通过抑制嘌呤能系统（E-NTPDase 和 E-ADA 活性）和 IFN-γ和 IL-4 的水平来调节关节炎的免疫反应。因此，这项工作与基础研究有关，可能转化为临床实践。
