2. Academic Validation
  3. Ginkgolide B Promotes Angiogenesis After Oxygen-Glucose Deprivation by Regulating AKT1 in bEnd.3 Cells

Ginkgolide B Promotes Angiogenesis After Oxygen-Glucose Deprivation by Regulating AKT1 in bEnd.3 Cells

  • Front Biosci (Landmark Ed). 2025 Dec 15;30(12):46724. doi: 10.31083/FBL46724.
Yuanchen Liao 1,  Lei Luo 1,  Qiang Ma 2 3,  Siyang Yan 2,  Menghao He 1,  Lijuan Liu 2,  Xiaofeng Gao 2,  Desheng Zhou 2,  Yao Chen 2
Affiliations

Affiliations

  • 1 The First School of Clinical Chinese Medicine, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China.
  • 2 Department of Neurology, The First Affiliated Hospital of Hunan University of Chinese Medicine, 410006 Changsha, Hunan, China.
  • 3 The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China.
PMID: 41504064 DOI: 10.31083/FBL46724
Abstract

Background: Ischemic stroke leads to significant neuronal damage, and impaired angiogenesis remains a critical factor limiting post-stroke recovery. Ginkgolide B (GB), a key component of Ginkgo biloba extract, has shown potential neuroprotective effects, but its pro-angiogenic mechanisms remain unclear.

Methods: To investigate the effects of GB, we established an oxygen-glucose deprivation/reperfusion (OGD/R) model using bEnd.3 cells. Potential molecular targets of GB were explored through a combination of network pharmacology analysis, protein-protein interaction (PPI) network construction, pathway enrichment, and molecular dynamics simulations. Based on these predictions, a series of in vitro assays-including Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, wound-healing, Transwell migration, and Matrigel tube formation tests-were performed to evaluate cell viability, proliferation, migration, and angiogenic activity. Western blotting was conducted to detect Akt serine/threonine kinase 1 (Akt1), vascular endothelial growth factor (VEGF), and Angiogenin (Ang) expression and clarify the role of the Akt1/VEGF/Ang pathway.

Results: Bioinformatics analysis identified 19 potential targets, among which Akt1, Matrix Metalloproteinase 9 (MMP9), and Prostaglandin-Endoperoxide Synthase 2 (PTGS2) exhibited the highest relevance. GB showed no evident cytotoxicity at concentrations up to 40 μM and mitigated the OGD/R-induced reduction in cell viability. At this concentration range, GB also enhanced endothelial proliferation, migration, and tube formation in bEnd.3 cells. Mechanistic studies revealed that MK2206 inhibition of Akt1 markedly suppressed Akt1 expression (p < 0.01), impaired angiogenic capacity, and aggravated ischemic-hypoxic injury, whereas GB treatment significantly increased VEGF and Ang expression (p < 0.01), likely via Akt1 upregulation (p < 0.01).

Conclusion: GB promotes angiogenesis and exerts neuroprotective effects by activating the Akt1/VEGF/Ang signaling pathway, suggesting its potential therapeutic value for ischemic stroke-related injuries.

Keywords

AKT1; Ginkgolide B; angiogenesis; ischemic stroke.

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