Blood-brain barrier breakdown and ROS overproduction are important events during the progression of ischemic stroke aggravating brain damage. Geraniol, a natural monoterpenoid, possesses anti-apoptotic, cytoprotective, anti-oxidant, and anti-inflammatory activities. Our study aimed to investigate the effect and underlying mechanisms of geraniol in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human brain microvascular endothelial cells (HBMECs). Apoptosis, caspase-3 activity, and cytotoxicity of HBMECs were evaluated using TUNEL, caspase-3 activity, and CCK-8 assays, respectively. The permeability of HBMECs was examined using FITC-dextran assay. Reactive oxygen species (ROS) production was measured using the fluorescent probe DCFH-DA. The protein levels of zonula occludens-1 (ZO-1), occludin, claudin-5, β-catenin, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were determined by western blotting. Geraniol showed no cytotoxicity in HBMECs. Geraniol and ROS scavenger N-acetylcysteine (NAC) both attenuated OGD/R-induced apoptosis and increase of caspase-3 activity and the permeability to FITC-dextran in HBMECs. Geraniol relieved OGD/R-induced ROS accumulation and decrease of expression of ZO-1, occludin, claudin-5, and β-catenin in HBMECs. Furthermore, we found that geraniol activated Nrf2/HO-1 pathway to inhibit ROS in HBMECs. In conclusion, geraniol attenuated OGD/R-induced ROS-dependent apoptosis and permeability in HBMECs through activating the Nrf2/HO-1 pathway.

血脑屏障破坏和活性氧过量产生是缺血性中风进展过程中的重要事件，会加剧脑损伤。香叶醇是一种天然单萜类化合物，具有抗凋亡、细胞保护、抗氧化和抗炎活性。我们的研究旨在探讨香叶醇在氧糖剥夺/复氧（OGD/R）诱导的人脑微血管内皮细胞（HBMEC）中的作用和潜在机制。分别使用 TUNEL、caspase-3 活性和 CCK-8 检测评估 HBMEC 的凋亡、caspase-3 活性和细胞毒性。使用 FITC-葡聚糖测定检查 HBMEC 的通透性。使用荧光探针 DCFH-DA 测量活性氧 (ROS) 的产生。采用 Western blot 法测定闭合小带 1 (ZO-1)、occludin、claudin-5、β-catenin、核因子红细胞 2 相关因子 2 (Nrf2) 和血红素加氧酶 -1 (HO-1) 的蛋白水平。印迹。香叶醇在 HBMEC 中没有表现出细胞毒性。香叶醇和 ROS 清除剂 N-乙酰半胱氨酸 (NAC) 均能减弱 OGD/R 诱导的细胞凋亡，并增加 HBMEC 中 caspase-3 活性和 FITC-葡聚糖的通透性。香叶醇可缓解 OGD/R 诱导的 ROS 积累以及 HBMEC 中 ZO-1、occludin、claudin-5 和 β-catenin 表达的降低。此外，我们发现香叶醇激活 Nrf2/HO-1 通路来抑制 HBMEC 中的 ROS。总之，香叶醇通过激活 Nrf2/HO-1 途径减弱 OGD/R 诱导的 HBMEC 中 ROS 依赖性细胞凋亡和通透性。