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从降香黄檀甲醇提取物中分离得到的新黄酮类化合物 latifolin 通过 Nrf2 介导的血红素加氧酶-1 表达抑制 NF-κB 激活,从而减轻炎症反应。

The neoflavonoid latifolin isolated from MeOH extract of Dalbergia odorifera attenuates inflammatory responses by inhibiting NF-κB activation via Nrf2-mediated heme oxygenase-1 expression.

机构信息

Hanbang Body Fluid Research Center, Wonkwang University, Iksan, 570-749, Korea.

出版信息

Phytother Res. 2014 Aug;28(8):1216-23. doi: 10.1002/ptr.5119. Epub 2014 Jan 29.

Abstract

In Korea and China, the heartwood of Dalbergia odorifera T. Chen is an important traditional medicine used to treat blood disorders, ischemia, swelling, and epigastric pain. In this study, we investigated the inhibitory effects of latifolin, a major neoflavonoid component isolated from the MeOH extract of D. odorifera, on the inflammatory reaction of thioglycollate-elicited peritoneal macrophages exposed to lipopolysaccharide, with a particular focus on heme oxygenase-1 (HO-1) expression and nuclear factor-κB (NF-κB) signaling. Latifolin significantly inhibited the protein and mRNA expression of inducible nitric oxide synthase and COX-2, reduced NO, prostaglandins E2, tumor necrosis factor-α, and interleukin-1β production in primary murine peritoneal macrophages exposed to lipopolysaccharide. Latifolin also suppressed inhibitor κB-α levels, NF-κB nuclear translocation, and NF-κB DNA-binding activity. Furthermore, latifolin upregulated HO-1 expression via nuclear transcription factor-E2-related factor 2 (Nrf2) nuclear translocation. In addition, using inhibitor tin protoporphyrin IX (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of latifolin on the proinflammatory mediators and NF-κB DNA-binding activity were associated with the HO-1 expression. These results suggested that the latifolin-mediated up-regulation of HO-1 expression played a critical role in anti-inflammatory effects in macrophages. This study therefore identified potent therapeutic effects of latifolin, which warrants further investigation as a potential treatment for inflammatory diseases.

摘要

在韩国和中国,降香黄檀的心材是一种重要的传统药物,用于治疗血液疾病、缺血、肿胀和胃脘痛。在这项研究中,我们研究了从降香黄檀甲醇提取物中分离得到的主要新黄酮成分 latifolin 对脂多糖诱导的巯基乙醇酸盐腹腔巨噬细胞炎症反应的抑制作用,特别是对血红素加氧酶-1 (HO-1) 表达和核因子-κB (NF-κB) 信号通路的影响。Latifolin 显著抑制诱导型一氧化氮合酶和 COX-2 的蛋白和 mRNA 表达,减少脂多糖诱导的原代小鼠腹腔巨噬细胞中 NO、前列腺素 E2、肿瘤坏死因子-α和白细胞介素-1β的产生。Latifolin 还抑制了 IκB-α 水平、NF-κB 核转位和 NF-κB DNA 结合活性。此外,latifolin 通过核转录因子-E2 相关因子 2 (Nrf2) 核转位上调 HO-1 表达。此外,使用 HO-1 抑制剂 tin 原卟啉 IX (SnPP) 验证了 latifolin 对促炎介质和 NF-κB DNA 结合活性的抑制作用与 HO-1 表达有关。这些结果表明,latifolin 介导的 HO-1 表达上调在巨噬细胞抗炎作用中发挥关键作用。因此,本研究鉴定了 latifolin 的潜在治疗作用,这使其有必要进一步作为炎症性疾病的潜在治疗方法进行研究。

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