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Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study

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Abstract

Objective

Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs.

Methods

An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings.

Results

Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage.

Conclusion

GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.

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Authors and Affiliations

  1. Department of Geriatrics, Peking University Traditional Chinese Medicine Clinical Medical School (**yuan), Bei**g, 100901, China

    Yi-miao Luo & Hao Li

  2. Department of Integration of Chinese and Western Medicine, Peking University Health Science Center, Bei**g, 100191, China

    Yi-miao Luo & Hao Li

  3. School of Pharmacy, Harbin University of Commerce, Harbin, 150028, China

    Shu-sen Liu

  4. **yuan Hospital, China Academy of Chinese Medical Science, Bei**g, 100901, China

    Ming Zhao & Yu Cao

  5. Wang**g Hospital, China Academy of Chinese Medical Science, Bei**g, 100102, China

    Wei Wei, Jiu-xiu Yao, Jia-hui Sun & Hao Li

Authors
  1. Yi-miao Luo
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  2. Shu-sen Liu
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  3. Ming Zhao
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  4. Wei Wei
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  5. Jiu-xiu Yao
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  7. Yu Cao
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  8. Hao Li
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Corresponding authors

Correspondence to Yu Cao or Hao Li.

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On behalf of all the authors, the corresponding author states that there is no conflict of interests.

Additional information

This study was funded by the Science and Technology Innovation Project of the China Academy of Chinese Medical Sciences (Nos. CI2021A04618 and CI2021A01401).

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Luo, Ym., Liu, Ss., Zhao, M. et al. Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study. CURR MED SCI 44, 578–588 (2024). https://doi.org/10.1007/s11596-024-2858-2

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  • DOI: https://doi.org/10.1007/s11596-024-2858-2

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