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Construction of 3D blood-brain barrier organoid oxygen-glucose deprivation model and exploration of the protective effect of Guanxinning injection
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Hong-ying DU1, 2, Zhi-feng XUE1, 2, Zhong-ting XIA1, 3, Shuang HE1, 2, Jian YANG1, 2, Yan ZHU1, 2, *
Acta Pharmaceutica Sinica | 2022, 57(10) : 3086 - 3094
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Acta Pharmaceutica Sinica | 2022, 57(10): 3086-3094
• Special Reports Ⅱ: Traditional Chinese Medicine in the Prevention and Treatment of Cardio-cerebrovascular Related Diseases •
Construction of 3D blood-brain barrier organoid oxygen-glucose deprivation model and exploration of the protective effect of Guanxinning injection
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Hong-ying DU1, 2, Zhi-feng XUE1, 2, Zhong-ting XIA1, 3, Shuang HE1, 2, Jian YANG1, 2, Yan ZHU1, 2, *
Affiliations
  • 1. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
  • 2. Chinese Medicine New Drug Research and Development Center, Tianjin International Biomedical Research Institute, Tianjin 300457, China
  • 3. Increasepharm (Tianjin) Institute Co., Ltd., Tianjin 300385, China
Published: 2022-10-12 doi: 10.16438/j.0513-4870.2021-1871
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The blood-brain barrier (BBB) plays an important role in maintaining the homeostasis of the central nervous system. BBB is disrupted in many neurological disorders such as ischemic stroke and Alzheimer's disease. Traditional Chinese medicine has great potential to prevent ischemic stroke, but the lack of clinically relevant models has been a challenge. We adapted a BBB organoid model formed by human brain microvascular endothelial cells (HBMEC), human astrocytes (HA), and human brain vascular pericytes (HBVP), and established conditions for oxygen-glucose deprivation/reoxygenation (OGD/R) on the cell vitality, barrier permeability, as well as BBB signature marker expression. The protective effect of Guanxinning injection (GXNI) on OGD/R-induced BBB dysfunction was then investigated in the organoid model. The results showed that OGD/R decreased BBB organoid cell viability, increased permeability (leakage), decreased the level of tight junction proteins zonula occludens-1 (ZO-1), claudin-5, occludin and P-glycoprotein (P-gp). GXNI significantly prevented OGD/R-induced BBB disruption such as the decreased cell viability and increased permeability. This study provides a new human cell-derived 3D ischemic brain disease model for central nervous system-targeted drug research and development and demonstrates that a Chinese injection medicine GXNI effectively protects BBB dysfunction in vitro.

blood-brain barrier  /  organoid  /  oxygen-glucose deprivation/reoxygenation  /  ischemic stroke  /  Guanxinning injection
Hong-ying DU, Zhi-feng XUE, Zhong-ting XIA, Shuang HE, Jian YANG, Yan ZHU. Construction of 3D blood-brain barrier organoid oxygen-glucose deprivation model and exploration of the protective effect of Guanxinning injection[J]. Acta Pharmaceutica Sinica, 2022 , 57 (10) : 3086 -3094 . DOI: 10.16438/j.0513-4870.2021-1871
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Year 2022 volume 57 Issue 10
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Article Info
doi: 10.16438/j.0513-4870.2021-1871
  • Receive Date：2021-12-31
  • Online Date：2025-12-24
  • Published：2022-10-12
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History
  • Received：2021-12-31
  • Revised：2022-02-28
Funding
Affiliations
    1. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
    2. Chinese Medicine New Drug Research and Development Center, Tianjin International Biomedical Research Institute, Tianjin 300457, China
    3. Increasepharm (Tianjin) Institute Co., Ltd., Tianjin 300385, China
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多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
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红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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