Kinsenoside alleviates oxidative stress-induced blood-brain barrier dysfunction via promoting Nrf2/HO-1 pathway in ischemic stroke

  • Eur J Pharmacol. 2023 Apr 11;949:175717. doi: 10.1016/j.ejphar.2023.175717.
Nan Qiao  1 ,  Zhaohong An  2 ,  Zeyu Fu  3 ,  Xingyu Chen  4 ,  Qingyi Tong  5 ,  Yonghui Zhang  6 ,  Hong Ren  7
Affiliations
  • 1. Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2. Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 3. Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
  • 4. Department of Clinical Laboratory, The Central Hospital of Wuhan, Wuhan, China.
  • 5. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
  • 6. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
  • 7. Biobank, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
PMID: 37054938 DOI: 10.1016/j.ejphar.2023.175717
Abstract

An ischemic stroke usually causes blood-brain barrier (BBB) damage and excessive oxidative stress (OS) levels. Kinsenoside (KD), a major effective compound extracted in Chinese herbal medicine Anoectochilus roxburghii (Orchidaceae), has anti-OS effects. The present study focused on exploring KD's protection against OS-mediated cerebral endothelial cell damage and BBB damage within the mouse model. Intracerebroventricular administration of KD upon reperfusion after 1 h ischemia decreased infarct volumes, neurological deficit, brain edema, neuronal loss, and Apoptosis 72 h post-ischemic stroke. KD improved BBB structure and function, as evidenced by a lower 18F-fluorodeoxyglucose pass rate of the BBB and upregulation of tight junction (TJ) proteins such as occludin, claudin-5, and zonula occludens-1 (ZO-1). KD protected bEnd.3 endothelial cells from oxygen and glucose deprivation/reoxygenation (OGD/R) injury in an in-vitro study. Meanwhile, OGD/R reduced transepithelial electronic resistance, whereas KD significantly increased TJ protein levels. Furthermore, based on in-vivo and in-vitro research, KD alleviated OS in endothelial cells, which is related to nuclear factor, erythroid 2 like 2 (Nrf2) nuclear translocation as well as Nrf2/haem oxygenase 1 signaling protein stimulation. Our findings demonstrated that KD might serve as a potential compound for treating ischemic stroke involving antioxidant mechanisms.

Keywords
Blood-brain barrier; Endothelial cell; Ischemic stroke; KD; Nrf2; Oxidative stress.
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