Coumarins are natural products with promising pharmacological activities owing to their anti-inflammatory, antioxidant, antiviral, anti-diabetic, and antimicrobial effects. Coumarins are present in many plants and microorganisms and have been widely used as complementary and alternative medicines. To date, the pharmacological efficacy of 4-hydroxy-7-methoxycoumarin (4H-7MTC) has not been reported yet. Therefore, in this study, we investigated the anti-inflammatory effects of 4H-7MTC in LPS-stimulated RAW264.7 cells as well as its mechanisms of action. Cells were treated with various concentrations of 4H-7MTC (0.3, 0.6, 0.9, and 1.2 mM) and 40 μM L-N6-(1-iminoethyl)-L-lysine (L-NIL) were used as controls. LPS-stimulated RAW264.7 cells showed that 4H-7MTC significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without cytotoxic effects. In addition, 4H-7MTC strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, 4H-7MTC reduced the production of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. We also found that 4H-7MTC strongly exerted its anti-inflammatory actions by downregulating nuclear factor kappa B (NF-κB) activation by suppressing inhibitor of nuclear factor kappa B alpha (IκBα) degradation in macrophages. Moreover, 4H-7MTC decreased phosphorylation of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK), but not that of p38 MAPK. These results suggest that 4H-7MTC may be a good candidate for the treatment or prevention of inflammatory diseases such as dermatitis, psoriasis, and arthritis. Ultimately, this is the first report describing the effective anti-inflammatory activity of 4H-7MTC.

中文翻译：

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4-Hydroxy-7-Methoxycoumarin 通过抑制 NF-κB 和 MAPK 激活来抑制 LPS 激活的 RAW264.7 巨噬细胞的炎症

香豆素是一种天然产物，具有抗炎、抗氧化、抗病毒、抗糖尿病和抗菌作用，具有良好的药理活性。香豆素存在于许多植物和微生物中，已被广泛用作补充和替代药物。迄今为止，4-羟基-7-甲氧基香豆素（4H-7MTC）的药理功效尚未见报道。因此，在本研究中，我们研究了 4H-7MTC 在 LPS 刺激的 RAW264.7 细胞中的抗炎作用及其作用机制。细胞用不同浓度的 4H-7MTC（0.3、0.6、0.9 和 1.2 mM）处理，40 μML-N6-（1-亚氨基乙基）-L-赖氨酸（L-NIL）用作对照。LPS 刺激的 RAW264。7 细胞显示 4H-7MTC 显着减少一氧化氮 (NO) 和前列腺素 E2 (PGE2) 的产生，而没有细胞毒性作用。此外，4H-7MTC 强烈降低诱导型一氧化氮合酶 (iNOS) 和环氧合酶 (COX-2) 的表达。此外，4H-7MTC 减少了促炎细胞因子的产生，如肿瘤坏死因子 (TNF)-α、白细胞介素 (IL)-1β 和 IL-6。我们还发现 4H-7MTC 通过抑制巨噬细胞中核因子 kappa B α (IκBα) 降解的抑制剂来下调核因子 kappa B (NF-κB) 的激活，从而强烈发挥其抗炎作用。此外，4H-7MTC 降低细胞外信号调节激酶 (ERK1/2) 和 c-Jun N 端激酶/应激激活蛋白激酶 (JNK) 的磷酸化，但不降低 p38 MAPK 的磷酸化。这些结果表明，4H-7MTC 可能是治疗或预防皮炎、银屑病和关节炎等炎症性疾病的良好候选者。最终，这是描述 4H-7MTC 有效抗炎活性的第一份报告。