Department of Neurology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Sep;397(9):6647-6659. doi: 10.1007/s00210-024-03045-3. Epub 2024 Mar 15.
Edaravone dexborneol (ED) is a novel neuroprotective compound that consists of two active ingredients, edaravone and ( +)-borneol in a 4:1 ratio, which has been shown the anti-inflammatory properties in animal models of ischemic stroke, cerebral hemorrhage, and autoimmune encephalomyelitis. However, the effect of ED on the polarization of microglia in neuroinflammation has not been elucidated. This study was to investigate the effects of ED on the polarization of microglia induced by lipopolysaccharide (LPS) and potential mechanisms. BV-2 microglial cells were incubated with ED (100, 200, and 400 µM) for 2 h, followed by lipopolysaccharide (LPS, 1 µg/ml) for 12 h. The researchers used the Griess method, western blot, immunocytochemistry, and subcellular fractionation to assess the effects and potential mechanisms of ED on neuroinflammatory reactions. The expression of ROS and the activities of antioxidant enzymes (SOD, GPx, and CAT) in LPS-induced BV-2 cells were also measured using the DCFH-DA fluorescent probe and colorimetric methods, respectively. It was observed that ED significantly declined the levels of TLR4/NF-κB pathway-associated proteins (TLR4, MyD88, p65, p-p65, IκBα, p-IκBα, IKKβ, p-IKKβ) and therefore inhibited LPS-induced production of NO, IL-1β, and TNF-α. Moreover, ED markedly downregulated the M1 marker (iNOS) and upregulated the M2 marker (Arginase-1, Ym-1). In addition, ED also reduced ROS generation and enhanced GPx activity. ED induced the polarization of LPS-stimulated microglia from M1 to M2 against inflammation by negatively regulating the TLR4/MyD88/NF-κB signaling pathway. Additionally, ED performed antioxidative function by depleting the intracellular excessive ROS caused by LPS through the enhancement of the enzymatic activity of GPx. ED may be a potential agent to attenuate neuroinflammation via regulating the polarization of microglia.
依达拉奉右莰醇（ED）是一种新型的神经保护化合物，由两种活性成分依达拉奉和（+）-冰片以 4:1 的比例组成，已在缺血性脑卒中、脑出血和自身免疫性脑脊髓炎的动物模型中显示出抗炎作用。然而，ED 对神经炎症中小胶质细胞极化的影响尚未阐明。本研究旨在探讨 ED 对脂多糖（LPS）诱导的小胶质细胞极化的影响及其潜在机制。将 BV-2 小胶质细胞用 ED（100、200 和 400 μM）孵育 2 小时，然后用脂多糖（LPS，1 μg/ml）孵育 12 小时。研究人员使用格里塞斯法、western blot、免疫细胞化学和亚细胞分离来评估 ED 对神经炎症反应的影响和潜在机制。还使用 DCFH-DA 荧光探针和比色法分别测量 LPS 诱导的 BV-2 细胞中 ROS 的表达和抗氧化酶（SOD、GPx 和 CAT）的活性。结果表明，ED 显著降低了 TLR4/NF-κB 通路相关蛋白（TLR4、MyD88、p65、p-p65、IκBα、p-IκBα、IKKβ、p-IKKβ）的水平，从而抑制了 LPS 诱导的 NO、IL-1β 和 TNF-α的产生。此外，ED 明显下调了 M1 标志物（iNOS）并上调了 M2 标志物（精氨酸酶-1、Ym-1）。此外，ED 还减少了 ROS 的产生并增强了 GPx 的活性。ED 通过负调控 TLR4/MyD88/NF-κB 信号通路，抑制 LPS 诱导的小胶质细胞从 M1 向 M2 极化，从而减轻炎症。此外，ED 通过增强 GPx 的酶活性来耗竭 LPS 引起的细胞内过多的 ROS，从而发挥抗氧化作用。ED 可能是通过调节小胶质细胞极化来减轻神经炎症的潜在药物。
