Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, P.O Box 812, Yaoundé, Cameroon.
Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China; Department of Biochemistry, Faculty of Science, University of Yaoundé I, P.O Box 812, Yaoundé, Cameroon.
Bioorg Chem. 2018 Oct;80:216-222. doi: 10.1016/j.bioorg.2018.06.021. Epub 2018 Jun 27.
Lambertellin (1) and ergosta-5,7,22-trien-3-ol (2) were isolated from the solid rice fermentation of the plant pathogenic fungus Pycnoporus sanguineus MUCL 51321. Their structures were elucidated using comprehensive spectroscopic methods. The isolated compounds were tested on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Lambertellin (1) exhibited promising inhibitory activity against nitric oxide (NO) production with IC value of 3.19 µM, and it significantly inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Lambertellin (1) also decreased the expression of pro-inflammatory cytokines IL-6 and IL-1β. The study of the mechanistic pathways revealed that lambertellin (1) exerts its anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophage cells by modulating the activation of the mitogen activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. Therefore, lambertellin (1) could be a promising lead compound for the development of new anti-inflammatory drugs.
从植物病原真菌 Pycnoporus sanguineus MUCL 51321 的固体大米发酵物中分离得到了 Lambertellin (1) 和麦角甾-5,7,22-三烯-3-醇 (2)。通过全面的光谱方法阐明了它们的结构。分离得到的化合物在脂多糖 (LPS) 刺激的 RAW 264.7 巨噬细胞中进行了测试。Lambertellin (1) 对一氧化氮 (NO) 生成表现出有希望的抑制活性，IC 值为 3.19 µM，并且它显著抑制诱导型一氧化氮合酶 (iNOS) 和环加氧酶 2 (COX-2) 的表达。Lambertellin (1) 还降低了促炎细胞因子 IL-6 和 IL-1β 的表达。对机制途径的研究表明，Lambertellin (1) 通过调节丝裂原激活蛋白激酶 (MAPK) 和核因子 κB (NF-κB) 信号通路的激活，在 LPS 刺激的 RAW 264.7 巨噬细胞中发挥抗炎作用。因此，Lambertellin (1) 可能是开发新型抗炎药物的有前途的先导化合物。
