Desoxyrhapontigenin up-regulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury.
Desoxyrhapontigenin up-regulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury.
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DOI：
10.1016/j.redox.2014.02.001
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发表时间：
2014
期刊：
影响因子：
11.4
通讯作者：
Shik Kim Y
中科院分区：
文献类型：
--
作者：
Joo Choi R;Cheng MS;Shik Kim Y
血红素加氧酶-1（HO-1）是一种重要的抗炎、抗氧化和细胞保护酶，受主要转录因子核因子（红细胞衍生2）样2（Nrf 2）的激活调控。本文报道了从波叶大黄中分离得到的六个二苯乙烯类化合物。评估其抗氧化潜力。在叔丁基过氧化氢（t-BHP）诱导的RAW 264.7巨噬细胞系中，脱氧漏芦皂苷元是减少细胞内活性氧（ROS）和过氧亚硝酸盐的最有效的成分。在响应desoxyrhapontigenin，抗氧化酶的mRNA表达水平上调。电泳迁移率变动分析（EMSA）证实，desoxyrhapontigenin促进Nrf 2的DNA结合，并增加抗氧化蛋白和酶的表达受Nrf 2调节。利用Akt、p38、JNK和ERK的特异性抑制剂的进一步研究表明，磷脂酰肌醇3-激酶（PI 3 K）/Akt途径介导HO-1的表达。此外，Nrf 2或Akt基因敲低可逆转脱氧漏芦配基处理介导的Nrf 2表达增加。在LPS诱导的体内肺部炎症模型中，去氧大黄素预处理显著改善LPS诱导的肺部炎症和组织学变化。进行了Nrf 2、HO-1和p65的免疫组织化学分析，证实用脱氧漏芦皂苷元处理诱导Nrf 2和HO-1表达，但降低p65表达。这些研究结果表明，desoxyrhapontigenin可能是一个潜在的治疗候选人作为抗氧化剂或抗炎剂。一种通过激活Nrf 2信号转导的脱氧大黄素诱导的Nrf/ARE介导的抗氧化基因上调的拟议途径。 脱氧漏芦配基对抗氧化酵素之提升作用。RAW 264.7巨噬细胞中Nrf 2的DNA结合亲和力的促进。脱氧大黄素通过Akt途径诱导HO-1表达和抑制Keap 1。改善LPS诱导的小鼠炎性肺损伤。
Heme oxygenase-1 (HO-1) is an important anti-inflammatory, antioxidative and cytoprotective enzyme that is regulated by the activation of the major transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In the present study, six stilbene derivatives isolated from Rheum undulatum L. were assessed for their antioxidative potential. In the tert-butylhydroperoxide (t-BHP)-induced RAW 264.7 macrophage cell line, desoxyrhapontigenin was the most potent component that reduced intracellular reactive oxygen species (ROS) and peroxynitrite. In response to desoxyrhapontigenin, the mRNA expression levels of antioxidant enzymes were up-regulated. An electrophoretic mobility shift assay (EMSA) confirmed that desoxyrhapontigenin promoted the DNA binding of Nrf2 and increased the expression of antioxidant proteins and enzymes regulated by Nrf2. Further investigation utilizing specific inhibitors of Akt, p38, JNK and ERK demonstrated that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediates HO-1 expression. Moreover, the increase in Nrf2 expression mediated by treatment with desoxyrhapontigenin was reversed by Nrf2 or Akt gene knock-down. In the LPS-induced in vivo lung inflammation model, pretreatment with desoxyrhapontigenin markedly ameliorated LPS-induced lung inflammation and histological changes. Immunohistochemical analysis of Nrf2, HO-1 and p65 was conducted and confirmed that treatment with desoxyrhapontigenin induced Nrf2 and HO-1 expression but reduced p65 expression. These findings suggest that desoxyrhapontigenin may be a potential therapeutic candidate as an antioxidant or an anti-inflammatory agent. A proposed pathway for desoxyrhapontigenin-induced Nrf/ARE-mediated up-regulation of antioxidant genes via the activation of Nrf2 signaling. Enhancement of the levels of antioxidant enzymes by desoxyrhapontigenin. Promotion of DNA binding affinity of Nrf2 in RAW 264.7 macrophages. Induction of HO-1 expression and inhibition of Keap1 by desoxyrhapontigenin via the Akt pathway. Amelioration of LPS-induced inflammatory lung injury in mice.
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影响因子：
2.4
作者：
Coppa, Tania;Lazze, Maria Claudia;Savio, Monica
通讯作者：
Savio, Monica
影响因子：
4.6
作者：
Jin, Wei;Wang, Handong;Yan, Wei;Xu, Lizhi;Wang, Xiaoliang;Zhao, Xiaoning;Yang, Xiaohe;Chen, Gang;Ji, Yan
通讯作者：
Ji, Yan
影响因子：
2
作者：
Kim, DH;Park, EK;Han, MJ
通讯作者：
Han, MJ
影响因子：
3.4
作者：
Kim, Jeong-Eun;Kim, Hye-Jin;Jeon, Jae-Gyu
通讯作者：
Jeon, Jae-Gyu
DOI：
10.1155/2012/974713
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Choi JY;Kwun MJ;Kim KH;Lyu JH;Han CW;Jeong HS;Ha KT;Jung HJ;Lee BJ;Sadikot RT;Christman JW;Jung SK;Joo M
通讯作者：
Joo M