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Abstract：
Various herbal extracts containing luteolin-7-O-glucuronide (L7Gn) have been traditionally used to treat inflammatory diseases. However, systemic studies aimed at elucidating the anti-inflammatory and anti-oxidative mechanisms of L7Gn in macrophages are insufficient. Herein, the anti-inflammatory and anti-oxidative effects of L7Gn and their underlying mechanisms of action in macrophages were explored. L7Gn inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by transcriptional regulation of inducible NO synthase (iNOS) in a dose-dependent manner. The mRNA expression of inflammatory mediators, including cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), was inhibited by L7Gn treatment. This suppression was mediated through transforming growth factor beta-activated kinase 1 (TAK1) inhibition that leads to reduced activation of nuclear factor-κB (NF-κB), p38, and c-Jun N-terminal kinase (JNK). L7Gn also enhanced the radical scavenging effect and increased the expression of anti-oxidative regulators, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1), by nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) activation. These results indicate that L7Gn exhibits anti-inflammatory and anti-oxidative properties in LPS-stimulated murine macrophages, suggesting that L7Gn may be a suitable candidate to treat severe inflammation and oxidative stress.
摘要：
传统上使用含有木犀草素-7-O-葡糖苷酸(L7Gn)的各种草药提取物来治疗炎性疾病。然而,旨在阐明L7Gn在巨噬细胞中的抗炎和抗氧化机制的系统性研究不足.在这里，研究了L7Gn的抗炎和抗氧化作用及其在巨噬细胞中的作用机制.L7Gn通过诱导型NO合酶（iNOS）的转录调节以剂量依赖性方式抑制脂多糖（LPS）刺激的RAW264.7巨噬细胞中一氧化氮（NO）的产生。炎症介质的mRNA表达，包括环氧合酶-2（COX-2），白细胞介素-6（IL-6），IL-1β,和肿瘤坏死因子-α（TNF-α），被L7Gn处理抑制。这种抑制是通过转化生长因子β激活的激酶1（TAK1）抑制介导的，从而导致核因子-κB（NF-κB）的活化降低，p38和c-JunN末端激酶(JNK)。L7Gn还增强了自由基清除作用并增加了抗氧化调节剂的表达，包括血红素加氧酶-1（HO-1），谷氨酸-半胱氨酸连接酶催化亚基（GCLC），和NAD（P）H醌氧化还原酶1（NQO1），通过核因子-红细胞2p45相关因子2（Nrf2）激活。这些结果表明，L7Gn在LPS刺激的鼠巨噬细胞中表现出抗炎和抗氧化特性，提示L7Gn可能是治疗严重炎症和氧化应激的合适候选者。
