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    The Protective Effect of Ginkgolide K on Astrocytes Exposed to Myelin Debris in vitro and Demyelination in vivo

    Xiao-Hui Li1, Ke-Xin Liu1, Zhi-Bin Ding2, Qing Wang1, Li-Juan Song1,3, Jie-Zhong Yu4, Dong Ma3, Bao-Guo Xiao5, Cun-Gen Ma1,4 Corresponding author

    1. 1Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, CHINA.
    2. 2Department of Neurosurgery, General Hospital, Datong Coalmine Group, Datong, CHINA.
    3. 3Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases,Institute of Brain Science, Shanxi Datong University, Datong, CHINA.
    4. 4Department of Neurology, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, CHINA.
    5. 5The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong, CHINA.

    CORRESPONDENCE

    Cun-Gen Ma

    Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, CHINA.

    macungen@sxtcm.edu.cn

    Received: 09-12-2022; Accepted: 29-03-2023.

    Volume 19, Issue 4 · pp. 811–821 · PUBLISHED 2023 · DOI: 10.1177/09731296231171454

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Background: Ginkgolide K (GK) has a protective effect on neurons and myelin sheath, and the function of astrocytes in phagocytizing myelin debris has attracted extensive attention in remyelination. Objectives: This study focuses on the impact of GK on the phagocytosis of myelin debris by astrocytes and explores the possibility of treating demyelination. Materials and Methods: Male C57BL/6 mice were used to establish a cuprizone (CPZ)-induced demyelination model. After being fed a normal or CPZ diet for 4 weeks, mice were intraperitoneally injected with PEG400 or GK for 14 consecutive days. GL261 and primary astrocytes were exposed to myelin debris. Immunohistochemistry/immunocytochemistry staining, western blot, RT-PCR, and other methods were used to detect the relevant indicators. Results: Astrocytes engulfed myelin debris, leading to astrocyte reactivity with increased p-NF-kB/p65 and ATF6 expression and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which was reversed by GK. Subsequently, astrocytes stimulated by myelin debris underwent self-apoptosis with increased expression of caspase-3 and BCL2-associated X (Bax), which was inhibited by GK. Simultaneously, GK efficiently promoted astrocytes to increase the production of neurotrophic ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF), speculating that increased CNTF/ bFGF, decreased p-NF-kB/p65/ATF6, and up-regulated Nrf2 should participate in the protection of astrocyte apoptosis and build a beneficial microenvironment for myelin regeneration. Conclusion: The results suggest that GK may have the potential to treat demyelination by promoting debris clearance and improving the brain microenvironment. However, further studies are needed to understand the physiological and pathological consequences of astrocytic phagocytosis and to investigate the possibility of using GK as a therapeutic application.

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      Li, X., Liu, K., Ding, Z., Wang, Q., Song, L., Yu, J., Ma, D., Xiao, B., & Ma, C. (2023). The Protective Effect of Ginkgolide K on Astrocytes Exposed to Myelin Debris in vitro and Demyelination in vivo. Pharmacognosy Magazine, 19(4), 811–821. https://doi.org/10.1177/09731296231171454