Gracilins are diterpenes derivative, isolated from the marine sponge Spongionella gracilis. Natural gracilins and synthetic derivatives have shown antioxidant, immunosuppressive, and neuroprotective capacities related to the affinity for cyclophilins. The aim of this work was to study anti-inflammatory and immunosuppressive pathways modulated by gracilin L and two synthetic analogues, compound 1 and 2, on a cellular model of inflammation. In this way, the murine BV2 microglia cell line was used. To carry out the experiments, microglia cells were pre-treated with compounds for 1 h and then stimulated with lipopolysaccharide for 24 h to determine reactive oxygen species production, mitochondrial membrane potential, the release of nitric oxide, interleukin-6 and tumor necrosis factor-α and the expression of Nuclear factor-erythroid 2-related factor 2, Nuclear Factor-κB, the inducible nitric oxide synthase, and the cyclophilin A. Finally, a co-culture of neuron SH-SY5Y and microglia BV2 cells was used to check the neuroprotective effect of these compounds. Cyclosporine A was used as a control of effect. The compounds were able to decrease inflammatory mediators, the expression of inflammatory target proteins as well as they activated anti-oxidative mechanism upon inflammatory conditions. For this reason, natural and synthetic gracilins could be interesting for developing anti-inflammatory drugs.

中文翻译：

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Gracilin衍生物作为抗炎作用的主要化合物。

Gracilins是二萜类衍生物，从海洋海绵海绵状海绵状杆菌中分离出来。天然gracilins和合成衍生物已显示出与亲环蛋白亲和力相关的抗氧化，免疫抑制和神经保护能力。这项工作的目的是在炎症细胞模型上研究由gracilin L和两种合成类似物化合物1和2调节的抗炎和免疫抑制途径。以这种方式，使用了鼠BV2小胶质细胞系。为了进行实验，将小胶质细胞用化合物预处理1小时，然后用脂多糖刺激24小时，以确定活性氧的产生，线粒体膜电位，一氧化氮的释放，白介素6和肿瘤坏死因子- α和核因子-类胡萝卜素2相关因子2的表达 核因子-κB，诱导型一氧化氮合酶和亲环蛋白A。最后，神经元SH-SY5Y和小胶质细胞BV2细胞的共培养物被用于检查这些化合物的神经保护作用。环孢菌素A用作对照。这些化合物能够减少炎症介质，炎症靶蛋白的表达以及在炎症条件下激活抗氧化机制。因此，天然和合成的gracilins对于开发抗炎药可能是有趣的。这些化合物能够减少炎症介质，炎症靶蛋白的表达以及在炎症条件下激活抗氧化机制。因此，天然和合成的gracilins对于开发抗炎药可能是有趣的。这些化合物能够减少炎症介质，炎症靶蛋白的表达以及在炎症条件下激活抗氧化机制。因此，天然和合成的gracilins对于开发抗炎药可能是有趣的。