Neuroprotective effect of ginkgetin in experimental cerebral ischemia/reperfusion via apoptosis inhibition and PI3K/Akt/mTOR signaling pathway activation
Abstract
BACKGROUND: Ginkgetin, extracted from Ginkgo biloba L leaves, has been demonstrated to have potential anti-inflammatory and immune-suppressive properties. But the neuroprotective effect and potential mechanisms of ginkgetin on cerebral ischemia/reperfusion (IR) injury remain unclear. METHODS: In this research, we studied the neuroprotective effect of ginkgetin in the middle part of the middle cerebral artery occlusion/reperfusion rat model, by analyzing the apoptosis of brain tissues harvested from treatment groups and control groups using the terminal deoxynucleotidyl transferase dUTP nick-end labeling and apoptosis assays. In addition, we detected the association of the neuroprotective effect of ginkgetin with apoptosis inhibition via the activation of the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway using Western blot analysis. RESULTS: Our results showed that administration of ginkgetin remarkably reduced brain infarction volumes and neurologic deficits; in addition, reducing apoptotic cell numbers, downregulating the levels of cleaved caspase-3 and Bax, and upregulating the level of Bcl-2 in rats subjected to IR injury in a dose-dependent manner. Moreover, high-dose ginkgetin treatment (100 mg/kg) significantly increased the phosphorylations of Akt and mTOR. Blocking of PI3K by LY294002 clearly decreased its antiapoptotic effect and reduced both Akt and mTOR phosphorylation levels. CONCLUSIONS: Taken together, these results for the first time suggest that ginkgetin antagonizes cerebral IR-induced injury by inhibiting apoptosis in rats, and this effect was attenuated by the activation of PI3K/Akt/mTOR signaling pathway.
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Ginkgetin shows neuroprotective activity by inhibiting neuro-inflammatory and apoptotic pathways.
“Recently, in a research conducted by Tian et al., ginkgetin, one of the bioflavones, has shown neuroprotective activity by inhibiting neuro-inflammatory and apoptotic pathways [97].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [97]
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- Authors
- Tian, Z., Tang, C., & Wang, Z.
- Affiliations
- Emergency Department Shenzhen Longgang District Hospital of Traditional Chinese Medicine Shenzhen P.R. China
- Corresponding author
- Tian, Zhaohua
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2019-07-02
- Volume
- 120
- Issue
- 10
- Pages
- 18487-18495
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2954245732
- Cited by
- 57
- References
- 30
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 8 · 2022: 9 · 2021: 4 · 2020: 9 · 2019: 1
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Ginkgo biloba and Cashew Applications
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- ginkgetin, Ginkgo biloba, neuroprotection, cerebral ischemia-reperfusion injury, apoptosis, PI3K/AKT/mTOR pathway, caspase-3, Bax, Bcl-2, middle cerebral artery occlusion, neurological deficit
- MeSH terms
- Animals, Brain Ischemia, Chromones, Enzyme Inhibitors, Male, Morpholines, Neurons, Random Allocation, Blotting, Western, Signal Transduction, Apoptosis, Neuroprotective Agents, Phosphatidylinositol 3-Kinases, Biflavonoids, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases
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