Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1-Nrf2-Are signaling pathway
Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1-Nrf2-Are signaling pathway
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穿心莲内酯通过激活 Keap1-Nrf2-Are 信号通路保护软骨细胞免受氧化应激损伤
DOI：
10.1002/jcp.26769
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Zhao, Jinmin
中科院分区：
文献类型：
--
作者：
Li, Bo;Jiang, Tongmeng;Zhao, Jinmin
最近的研究表明，雄激素（AP）有可能开发为骨关节炎治疗的药物（OA）。但是，AP在减弱OA进展中的作用仍然未知。我们假设其治疗作用可能与其抗氧化潜力有关。在这项研究中，我们通过检测细胞增殖，细胞活力，氧化应激特异性基因的表达（SOD1，CAD1，CAT和Malonaldehyde [Mda]和protoxians can）（Supteroxine can）（SupteroxiDe can），研究了AP对H2O2伤害的软骨细胞的治疗作用，以及与氧化有关的信号传导途径的关联。培养期分别为3天和5天。还进一步探索了核因子2相关因子2（NRF2）信使RNA和蛋白质的表达。结果表明，通过增加H2O2和包括SOD和CAT在内的H2O2和抗氧化酶活性，通过增加细胞增殖和抗氧化酶活性，AP的0.625 mu g/mL和2.5 mu g/ml的AP降低了软骨细胞的氧化应激损伤。在H2O2组中，炎症因子，例如基质金属肽酶13（MMP13），金属蛋白酶1（TIMP1）和白介素-6（IL6）的组织抑制剂在AP中下调，表明OA进展的降低。途径分析表明，类似Kelch的ECH相关蛋白1（KEAP1）-NRF2-抗氧化反应元件（AS）途径是H2O2诱导的OA的AP疗法的重要介体。这项研究表明，AP通过激活H2O2损伤的软骨细胞中的Keap1-Nrf2-ARE途径对氧化应激产生影响，这对于OA治疗可能有望。
Recent studies have shown that andrographolide (AP) has the potential to be developed as a drug for therapy for osteoarthritis (OA). However, the role of AP in attenuating the progression of OA is still unknown. We hypothesized that its therapeutic effect may be associated with its antioxidant potential. In this study, we investigated the therapeutic effect of AP on chondrocytes injured by H2O2 and the association with the oxidation-related signaling pathways through the detection of cell proliferation, cell viability, the expression of oxidative stress-specific genes (Sod1, Cat, and malonaldehyde [Mda]) and proteins (superoxide dismutase [SOD], catalase [CAT]) after a culture period of 3 and 5 days, respectively. Further exploration of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)messenger RNA and protein was also performed. The results showed that 0.625 mu g/ml and 2.5 mu g/ml of AP decreased oxidative stress injury of chondrocytes by increasing cell proliferation reduced by H2O2 and antioxidant enzyme activity, including SOD and CAT. Inflammation factors, such as matrix metallopeptidase 13 (Mmp13), tissue inhibitor of metalloproteinase 1 (Timp1), and interleukin-6 (Il6), were downregulated in the H2O2 group with AP, demonstrating a decrease in the progression of OA. Pathway analyses identified that the kelch-like ECH-associated protein 1 (Keap1)-Nrf2-antioxidant response element (Are) pathway is an important mediator in AP therapy on H2O2-induced OA. This study indicates that AP exerts protection effects on oxidative stress via activation of the Keap1-Nrf2-Are pathway in chondrocytes injured by H2O2, which may be promising for the therapy of OA.