Synergistic enhancement and hepatoprotective effect of combination of total phenolic extracts of Citrus aurantium L. and methotrexate for treatment of rheumatoid arthritis
Synergistic enhancement and hepatoprotective effect of combination of total phenolic extracts of Citrus aurantium L. and methotrexate for treatment of rheumatoid arthritis
复制标题
枳壳总酚提取物与甲氨蝶呤联合治疗类风湿关节炎的协同增强及保肝作用。
DOI：
10.1002/ptr.6306
复制
发表时间：
2019-04-01
影响因子：
7.2
通讯作者：
Liu, Yuanyan
中科院分区：
文献类型：
--
作者：
He, Dan;Liu, Zhenli;Liu, Yuanyan
类风湿性关节炎（RA）是一种以关节破坏和骨损伤为特征的自身免疫性炎症性疾病。甲氨蝶呤（MTX）被推荐作为治疗类风湿性关节炎的一线疾病调节剂。然而甲氨蝶呤由于其低反应和副作用，尤其是肝毒性，临床疗效有限。柑橘金酸（Citrus aurantium L.）总酚提取物（TPE-CA）富含膳食生物活性黄酮类化合物，对肝脏健康有益，被认为是治疗炎症性疾病的工具。本研究探讨MTX单用或联用TPE-CA对大鼠胶原性关节炎的治疗作用及对肝损伤的保护作用。TPE-CA联合MTX通过抑制NF-B通路，有效减轻炎症症状和关节损伤。此外，TPE-CA通过增强抗氧化酶活性、抑制肝细胞色素P450 2E1表达、调节核因子红系2相关因子2/血红素加氧酶-1通路，显著改善mtx诱导的慢性肝损伤。该联合方案不仅具有协同增强作用，而且对化学诱导的慢性肝毒性具有肝保护作用。这可能是改善甲氨蝶呤治疗RA低反应的另一种策略。
Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by joint destruction and bone damage. Methotrexate (MTX) is recommended as the first-line disease-modifying agent for the treatment of RA. However, the clinical efficacy of MTX is limited due to its low response and side effects, especially hepatotoxicity. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary bioactive flavonoids, which show beneficial effects on liver health and are regarded as therapeutic tools against inflammatory diseases. In this study, the efficacy of MTX, alone or in combination with TPE-CA, for the treatment of collagen-induced arthritis and protection against hepatic injury in rats was investigated. TPE-CA and MTX combination effectively reduced the inflammatory symptoms and joint damage by inhibiting the NF-B pathway. Moreover, TPE-CA significantly ameliorated MTX-induced chronic hepatic injury by enhancing antioxidant enzymes activities, suppressing hepatic cytochrome P450 2E1 expression, and modulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. This combination regimen not only provided synergistic enhancement but also exhibited hepatoprotective effect against chemically induced chronic hepatotoxicity. This could be an alternative strategy to improve the low response of MTX in RA treatment.