ArticleActa pharmacologica Sinica2018
Diterpene ginkgolides protect against cerebral ischemia/reperfusion damage in rats by activating Nrf2 and CREB through PI3K/Akt signaling.
Article in Acta pharmacologica Sinica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Natural herbal extract roles and mechanisms in treating cerebral ischemia: A systematic review.Frontiers in pharmacology · 2024Pooled it
- Effect of ginkgo diterpene lactone meglumine on the quality of life in patients with acute ischemic stroke.Health and quality of life outcomes · 2024Trial
- Efficacy of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke: a predefined exploratory analysis of a multicenter, double-blind, randomized controlled trial.Journal of neurology · 2024Trial
- Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke: A Randomized Clinical Trial.JAMA network open · 2023Trial
- Ginkgo biloba L. in preventing cardiovascular disease: pharmacological effects, mechanism of action, and therapeutic potential.Acta pharmacologica Sinica · 2026Review
- N-acetylcysteine alleviates experimental autoimmune prostatitis in rats by activating PI3K/Akt/CREB and Keap1/Nrf2 pathways.Translational andrology and urology · 2026Article
- Neuroprotection by canagliflozin in a Huntington's disease model: role of HIF-1α and PI3K/AKT signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Ginkgolide B regulates apoptosis, oxidative stress, and mitochondrial dysfunction in MPPNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Deciphering the Neuroprotective Action of Bee Venom Peptide Melittin: Insights into Mechanistic Interplay.Molecular neurobiology · 2025Review
- Roles of microRNAs in cardiorenal syndrome.Molecular and cellular biochemistry · 2025Review
- Article
- Activation of the Nrf2/Keap1 signaling pathway mediates the neuroprotective effect of Perillyl alcohol against cerebral hypoxic-ischemic damage in neonatal rats.Redox report : communications in free radical research · 2024Article
- Exploring the multifaceted role of ginkgolides and bilobalide fromFood science and biotechnology · 2024Review
- Plant-Derived Terpenoids: A Plethora of Bioactive Compounds with Several Health Functions and Industrial Applications-A Comprehensive Overview.Molecules (Basel, Switzerland) · 2024Review
- Review
- NRF2 activation ameliorates blood-brain barrier injury after cerebral ischemic stroke by regulating ferroptosis and inflammation.Scientific reports · 2024Article
- Neurotrophic Natural Products.Progress in the chemistry of organic natural products · 2024Article
- Targeting post-stroke neuroinflammation with Salvianolic acid A: molecular mechanisms and preclinical evidence.Frontiers in immunology · 2024Review
- Emerging Role of Plant-Based Bioactive Compounds as Therapeutics in Parkinson's Disease.Molecules (Basel, Switzerland) · 2023Review
- Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats.Chinese journal of integrative medicine · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diterpene ginkgolides meglumine injection (DGMI) is a therapeutic extract of Ginkgo biloba L, which has been used for the treatment of cerebral ischemic stroke in China. Ginkgolides A, B and C are the main components of DGMI. This study was designed to investigate the neuroprotective effects of DGMI components against ischemic stroke in vivo and in vitro. Acute cerebral ischemic injury was induced in rats by occlusion of the middle cerebral artery (MCA) for 1.5 h followed by 24 h reperfusion. The rats were treated with DGMI (1, 3 and 10 mg/kg, iv) at the onset of reperfusion and 12 h after reperfusion. Administration of DGMI significantly decreased rat neurological deficit scores, reduced brain infarct volume, and induced protein kinase B (Akt) phosphorylation, which prompted the nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and phosphorylation of the survival regulatory protein cyclic AMP-responsive element binding protein (CREB). Nrf2 activation led to expression of the downstream protein heme oxygenase-1 (HO-1). In addition, PC12 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) in vitro, treatment with DGMI (1, 10 and 20 μg/mL) or ginkgolides A, B or C (10 μmol/L for each) significantly reduced PC12 cell death and increased phosphorylation of Akt, nuclear translocation of Nrf2 and activation of CREB. Activation of Nrf2 and CREB could be reversed by co-treatment with a phosphoinositide-3-kinase (PI3K) inhibitor LY294002. These observations suggest that ginkgolides act as novel extrinsic regulators activating both Akt/Nrf2 and Akt/CREB signaling pathways, protecting against cerebral ischemia/reperfusion (I/R) damage in vivo and in vitro.
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