Department of Oral Physiology, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, Korea.
Int J Mol Sci. 2022 Apr 4;23(7):4004. doi: 10.3390/ijms23074004.
Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against neuroinflammation. However, the effects of EGCG on hypoxia-induced inflammation in microglia and the underlying mechanism remain unclear. In this study, we investigated whether EGCG might have a protective effect against hypoxia injury in microglia by treatment with CoCl to establish a hypoxic model of BV2 microglia cells following EGCG pre-treatment. An exposure of cells to CoCl caused an increase in inflammatory mediator interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 expression, which were significantly ameliorated by EGCG via inhibition of NF-κB pathway. In addition, EGCG attenuated the expression of hypoxia-inducible factor (HIF)-1α and the generation of ROS in hypoxic BV2 cells. Furthermore, the suppression of hypoxia-induced IL-6 production by EGCG was mediated via the inhibition of HIF-1α expression and the suppression of ROS generation in BV2 cells. Notably, EGCG increased the Nrf-2 levels and HO-1 levels in the presence of CoCl. Additionally, EGCG suppressed hypoxia-induced apoptosis of BV2 microglia with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3. In summary, EGCG protects microglia from hypoxia-induced inflammation and oxidative stress via abrogating the NF-κB pathway as well as activating the Nrf-2/HO-1 pathway.
缺氧诱导的神经炎症在中风、新生儿缺氧性脑病和其他疾病中随后导致神经损伤和神经元疾病。小胶质细胞是主要的神经免疫细胞，在大脑炎症中发挥关键作用。表没食子儿茶素没食子酸酯 (EGCG) 具有抗氧化和抗炎作用，可对抗神经炎症。然而，EGCG 对小胶质细胞缺氧诱导的炎症的影响及其潜在机制尚不清楚。在这项研究中，我们通过用 CoCl 处理来研究 EGCG 是否可能对小胶质细胞的缺氧损伤具有保护作用，以建立 EGCG 预处理后 BV2 小胶质细胞缺氧模型。细胞暴露于 CoCl 会导致炎症介质白细胞介素 (IL)-6、诱导型一氧化氮合酶 (iNOS) 和环氧化酶 (COX)-2 的表达增加，而 EGCG 通过抑制 NF-κB 途径显著改善了这种情况。此外，EGCG 减弱了缺氧 BV2 细胞中缺氧诱导因子 (HIF)-1α 和活性氧 (ROS) 的表达。此外，EGCG 通过抑制 HIF-1α 表达和抑制 ROS 生成来抑制缺氧诱导的 IL-6 产生。值得注意的是，EGCG 在 CoCl 存在的情况下增加了 Nrf-2 水平和 HO-1 水平。此外，EGCG 抑制了缺氧诱导的 BV2 小胶质细胞凋亡，减少了聚 (ADP-核糖) 聚合酶 (PARP) 和半胱天冬酶-3 的裂解。总之，EGCG 通过阻断 NF-κB 途径以及激活 Nrf-2/HO-1 途径来保护小胶质细胞免受缺氧诱导的炎症和氧化应激。
