Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation.

Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation.
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DOI:
10.1155/2012/974713
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发表时间:
2012
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Joo M
Joo M
中科院分区:
其他
文献类型:
--
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

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皂荚的果实船体(FGS)已被规定为治疗各种呼吸系统疾病的传统东亚药物,但其功效和潜在机制仍不清楚。在这里,我们探索了FGS用于治疗急性肺损伤(ALI)的潜在用途,急性肺损伤是一种高度致命的炎症性肺部疾病,迫切需要有效的治疗方法,并研究了FGS抗炎活性的机制。与假处理的发炎小鼠相比,用FGS预处理的C57 BL/6小鼠显著减弱LPS诱导的嗜酸性肺炎症。报告基因分析、半定量RT-PCR和Western blot分析表明,在RAW 264.7细胞中,FGS激活了Nrf 2,并表达了Nrf 2调控的基因,包括GCLC、NQO-1和HO-1,但不影响NF-κB。此外,小鼠用FGS预处理增强了炎症肺中GCLC和HO-1的表达,但抑制了促炎细胞因子(包括TNF-α和IL-1β)的表达。这些结果表明,FGS有效地抑制了嗜酸性肺部炎症,这可能与至少部分地FGS激活抗炎因子Nrf 2有关。我们的研究结果表明,FGS可以开发为治疗ALI的治疗选择。
The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI.
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