Chromatographic purification of Sigesbeckia glabrescens extracts led to three undescribed ent-pimarane diterpenoid dimers, named glabreside A—C (1—3). Their structures were confirmed by comprehensive spectroscopic analyses, and the structures of compound 1 and 3 were confirmed by X-ray crystallography. The results of anti-inflammatory activity assay showed that glabreside C (3) exhibited the most potent inhibition activity on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV2 microglia compared with the other two compounds. Glabreside C also increased the protein expression level of heme oxygenase-1 (HO-1), and suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in LPS-stimulated BV2 cells. Mechanistically, glabreside C exerts its anti-inflammatory effect by inhibiting AKT/MAPKs signaling pathway. These findings indicate the vital role of ent-pimarane diterpenoid dimers in explaining the anti-inflammatory activity of S. glabrescens and provide important evidence for further development and utilization of Sigesbeckiae Herba. These results also suggest that glabreside C is a potential lead compound for anti-inflammatory drugs.

中文翻译：

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来自 Sigesbeckia glabrescens 的 ent-Pimarane Diterpenoid 二聚体，具有强效抗炎活性

Sigesbeckia glabrescens提取物的色谱纯化导致三个未描述的ent-pimarane 二萜二聚体，命名为 glabreside A-C (1-3)。它们的结构通过综合光谱分析得到证实，化合物 1 和 3 的结构通过 X 射线晶体学得到证实。抗炎活性测定结果表明，与其他两种化合物相比，光甘草苷 C (3) 对脂多糖 (LPS) 在 BV2 小胶质细胞中诱导的一氧化氮 (NO) 产生表现出最有效的抑制活性。Glabreside C 还增加了血红素加氧酶-1 (HO-1) 的蛋白质表达水平，并抑制了 LPS 刺激的 BV2 细胞中的诱导型一氧化氮合酶 (iNOS) 和环氧合酶 2 (COX2)。从机制上讲，glabreside C 通过抑制 AKT/MAPKs 信号通路发挥其抗炎作用。这些发现表明耳鼻喉科的重要作用-pimarane diterpenoid 二聚体在解释S. glabrescens的抗炎活性方面，并为 Sigesbeckiae Herba 的进一步开发和利用提供重要证据。这些结果还表明，glabreside C 是抗炎药物的潜在先导化合物。