3α-Angeloyloxy-ent-kaur-16-en-19-oic Acid Isolated from Wedelia trilobata L. Alleviates Xylene-Induced Mouse Ear Edema and Inhibits NF-κB and MAPK Pathway in LPS-Stimulated Macrophages,Journal of Natural Products

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3α-Angeloyloxy-ent-kaur-16-en-19-oic Acid Isolated from Wedelia trilobata L. Alleviates Xylene-Induced Mouse Ear Edema and Inhibits NF-κB and MAPK Pathway in LPS-Stimulated Macrophages
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-12-11 , DOI: 10.1021/acs.jnatprod.0c00990
Jingwen Xu _{1,

2} , Lei Zhou ₁ , Lianlian Sun ₁ , Zhe Wang ₁ , Yi Wang ₁ , Yihai Wang _{1,

2} , Xiangjiu He _{1,

2}

Affiliation

Uncontrolled inflammation is associated with many major diseases, and there is still an urgent need to develop new anti-inflammatory drugs. 3α-Angeloyloxy-ent-kaur-16-en-19-oic acid (WT-25) is an ent-kaurane dieterpenoid extracted from Wedelia trilobata, a medicinal plant with potential anti-inflammatory activity. The anti-inflammatory activity of WT-25 is better than that of its analog kaurenoic acid, but the underlying mechanism is still unknown. In this study, our aim was to study the anti-inflammatory effect of WT-25. In xylene-induced edema in mice, WT-25 produced 51% inhibition. WT-25 suppressed nitric oxide (NO) and prostaglandin E2 (PGE₂) production in LPS-stimulated RAW264.7 cells by downregulating the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). WT-25 reduced expression and secretion of TNF-α and IL-6. Moreover, WT-25 inhibited NF-κB activation and its upstream signaling, decreasing phosphorylation IKK and p65 levels. WT-25 also inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) family. Additionally, it reduced LPS-induced excessive release of reactive oxygen species (ROS) and maintained mitochondrial integrity in RAW264.7 cells. All these results indicate that WT-25 is a bioactive molecule with the potential to be developed as a novel structured anti-inflammatory drug.

中文翻译：

从 Wedelia trilobata L. 中分离的 3α-Angeloyloxy-ent-kaur-16-en-19-oic Acid 减轻二甲苯诱导的小鼠耳水肿并抑制 LPS 刺激的巨噬细胞中的 NF-κB 和 MAPK 通路

不受控制的炎症与许多重大疾病有关，仍然迫切需要开发新的抗炎药物。3α-Angeloyloxy- ent -kaur-16-en-19-oic acid (WT-25) 是一种从Wedelia trilobata 中提取的ent- kaurane 二萜类化合物，Wedelia trilobata是一种具有潜在抗炎活性的药用植物。WT-25 的抗炎活性优于其类似物贝壳杉酸，但其潜在机制尚不清楚。在这项研究中，我们的目的是研究 WT-25 的抗炎作用。在二甲苯诱导的小鼠水肿中，WT-25 产生了 51% 的抑制作用。WT-25 抑制一氧化氮 (NO) 和前列腺素 E2 (PGE ₂) 通过下调一氧化氮合酶 (iNOS) 和环氧合酶-2 (COX-2) 的表达，在 LPS 刺激的 RAW264.7 细胞中产生。WT-25 减少 TNF-α 和 IL-6 的表达和分泌。此外，WT-25 抑制 NF-κB 活化及其上游信号，降低磷酸化 IKK 和 p65 水平。WT-25 还抑制丝裂原活化蛋白激酶 (MAPK) 家族的磷酸化。此外，它还减少了 LPS 诱导的活性氧 (ROS) 过度释放并保持了 RAW264.7 细胞中的线粒体完整性。所有这些结果表明 WT-25 是一种生物活性分子，具有开发为新型结构抗炎药的潜力。

更新日期：2020-12-24

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