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Geraniol attenuates oxygen-glucose deprivation/reoxygenation-induced ROS-dependent apoptosis and permeability of human brain microvascular endothelial cells by activating the Nrf-2/HO-1 pathway

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Abstract

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.

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Acknowledgements

This research was supported by the Basic Scientific Research Fund Project of Huai’an Second People’s Hospital (HAEY202403).

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  1. Ronggang Yang and Feng Yan contributed equally to this work.

Authors and Affiliations

  1. Department of Neurological Intensive Resuscitation, Nanshi Hospital of Nanyang, Nanyang, 473000, China

    Ronggang Yang & Feng Yan

  2. Department of Critical Care Medicine, Nanshi Hospital of Nanyang, Nanyang, 473000, China

    Jiangyi Shen, Tiancai Wang & Menglong Li

  3. Department of Neurosurgery, Huai’an Second People’s Hospital, the Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, 223300, China

    Hongzao Ni

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  1. Ronggang Yang
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Ronggang Yang performed experiments and wrote the manuscript. Feng Yan performed experiments. Jiangyi Shen and Tiancai Wang contributed to data collection and analysis. Menglong Li and Hongzao Ni contributed to conception and supervision. All authors reviewed the manuscript.

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Yang, R., Yan, F., Shen, J. et al. Geraniol attenuates oxygen-glucose deprivation/reoxygenation-induced ROS-dependent apoptosis and permeability of human brain microvascular endothelial cells by activating the Nrf-2/HO-1 pathway. J Bioenerg Biomembr 56, 193–204 (2024). https://doi.org/10.1007/s10863-024-10011-4

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