New compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton from Clematis mandshurica: Anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglial cells.
New compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton from Clematis mandshurica: Anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglial cells.
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DOI：
10.1016/j.intimp.2014.10.030
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发表时间：
2015
影响因子：
5.6
通讯作者：
M. G. Dilshara;Kyoung-tae Lee;Chang‐Min Lee;Yung-Hyun Choi;Hak-ju Lee;I. Choi;Gi-Young Kim
中科院分区：
文献类型：
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作者：
M. G. Dilshara;Kyoung-tae Lee;Chang‐Min Lee;Yung-Hyun Choi;Hak-ju Lee;I. Choi;Gi-Young Kim
小胶质细胞是持续性过度激活的主要免疫细胞，可加重神经系统疾病。因此，调控小胶质细胞是治疗神经系统疾病的有效策略。本研究从东北铁线莲中分离并鉴定了一个新化合物5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton（5-DRL），并在脂多糖（LPS）处理的BV2小胶质细胞中评价了其抗炎作用。5-DRL抑制LPS刺激的促炎介质如一氧化氮（NO）和前列腺素E2（PGE 2）及其调节基因诱导型NO合成酶（iNOS）和环氧合酶-2（考克斯-2）的表达。5-DRL还通过抑制NF-κ B亚基、p65和p50的核转位来下调LPS诱导的核因子-κ B（NF-κ B）的DNA结合活性。与5-DRL通过NF-κ B活性抑制NO和COX-2表达一致，NF-κ B抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）也可抑制LPS诱导的NO和COX-2表达。此外，5-DRL对应的抗氧化剂，N-乙酰半胱氨酸（NAC）和谷胱甘肽（GSH），显着抑制活性氧（ROS）的产生。NAC和GSH均通过抑制NF-κ B的活化而抑制NO和COX-2的表达，表明5-DRL通过下调ROS依赖的NF-κ B信号通路而抑制LPS诱导的NO和COX-2的表达。本研究还表明，5-DRL通过核因子红细胞2相关因子2（Nrf2）诱导血红素加氧酶-1（HO-1）来抑制NO和PGE 2的产生。综上所述，目前的数据表明，5-DRL通过抑制ROS依赖的NF-κ B活化和刺激Nrf2/HO-1信号通路，减少LPS刺激的BV2小胶质细胞中促炎介质如NO和PGE2及其调节基因的产生。这些数据可能与5-DRL在LPS刺激的炎症性疾病中的应用有关。
Microglia are main immune cells to exacerbate neural disorders in persistent overactivating. Therefore, it is a good strategy to regulate microglia for the treatment of neural disorders. In the present study, we isolated and characterized a novel compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton (5-DRL) fromClematis mandshurica, and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-treated BV2 microglial cells. 5-DRL inhibited the expression of LPS-stimulated proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2(PGE2), as well as their regulatory genesinducible NO syntheses(iNOS) andcyclooxygenase-2(COX-2). 5-DRL also downregulated the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of the nuclear translocation of the NF-κB subunits, p65 and p50. Consistent with the inhibition ofiNOSandCOX-2via NF-κB activity with 5-DRL, an inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), also led to the suppression of LPS-inducediNOSandCOX-2expression. Additionally, 5-DRL corresponding with antioxidants,N-acetylcysteine (NAC) and glutathione (GSH), remarkably inhibited reactive oxygen species (ROS) generation. Both NAC and GSH, thus attenuated the expression ofiNOSandCOX-2by suppressing NF-κB activation, indicating that 5-DRL suppresses LPS-inducediNOSandCOX-2expression through downregulation of the ROS-dependent NF-κB signaling pathway. The present study also indicated that 5-DRL suppresses NO and PGE2production by inducing heme oxygenase-1 (HO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, the present data indicate that 5-DRL attenuates the production of proinflammatory mediators such as NO and PGE2as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting ROS-dependent NF-κB activation and stimulating the Nrf2/HO-1 signal pathway. These data may be implicated in the application of 5-DRL in LPS-stimulated inflammatory disease.