ArticleFrontiers in neuroanatomy2015
Neuroprotective effects of DAHP and Triptolide in focal cerebral ischemia via apoptosis inhibition and PI3K/Akt/mTOR pathway activation.
Article in Frontiers in neuroanatomy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Effects of triptolide herb on the progression of Alzheimer's disease preclinical models: a systematic review.Neurodegenerative disease management · 2026Pooled it
- Neuroprotection by canagliflozin in a Huntington's disease model: role of HIF-1α and PI3K/AKT signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The Emerging Role of Adropin in Neurological Health: A Systematic Review.Iranian journal of public health · 2025Review
- Pharmacological modulation of PI3K/PTEN/Akt/mTOR/ERK signaling pathways in ischemic injury: a mechanistic perspective.Metabolic brain disease · 2025Review
- Exploring research trends and hotspots in PI3K/Akt signaling pathway in ischemic stroke: a bibliometric analysis.Frontiers in molecular neuroscience · 2025Article
- Hypericin alleviates cerebral ischemia/reperfusion injury by modulating endoplasmic reticulum stress.Frontiers in pharmacology · 2025Article
- Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization.Science China. Life sciences · 2024Article
- Nrf2 Pathway in Huntington's Disease (HD): What Is Its Role?International journal of molecular sciences · 2022Review
- Tetrahydrobiopterin in Cell Function and Death Mechanisms.Antioxidants & redox signaling · 2022Review
- Insulin-like Growth Factor 1 Promotes Cell Proliferation by Downregulation of G-Protein-Coupled Receptor 17 Expression via PI3K/Akt/FoxO1 Signaling in SK-N-SH Cells.International journal of molecular sciences · 2022Article
- Triptolide protects against white matter injury induced by chronic cerebral hypoperfusion in mice.Acta pharmacologica Sinica · 2022Article
- The therapeutic potential of triptolide and celastrol in neurological diseases.Frontiers in pharmacology · 2022Review
- Investigation of blood leptin and adropin levels in patients with multiple sclerosis: A CONSORT-clinical study.Medicine · 2021Article
- Tetrandrine attenuates ischemia/reperfusion‑induced neuronal damage in the subacute phase.Molecular medicine reports · 2021Article
- Inhibition of Brain GTP Cyclohydrolase I Attenuates 3-Nitropropionic Acid-Induced Striatal Toxicity: Involvement of Mas Receptor/PI3k/Akt/CREB/ BDNF Axis.Frontiers in pharmacology · 2021Article
- Inflammation-Mediated Angiogenesis in Ischemic Stroke.Frontiers in cellular neuroscience · 2021Review
- Iridoid glycosides from Radix Scrophulariae attenuates focal cerebral ischemia‑reperfusion injury via inhibiting endoplasmic reticulum stress‑mediated neuronal apoptosis in rats.Molecular medicine reports · 2020Article
- Inhibited CSF1R Alleviates Ischemia Injury via Inhibition of Microglia M1 Polarization and NLRP3 Pathway.Neural plasticity · 2020Article
- Combinational Pretreatment of Colony-Stimulating Factor 1 Receptor Inhibitor and Triptolide Upregulates BDNF-Akt and Autophagic Pathways to Improve Cerebral Ischemia.Mediators of inflammation · 2020Article
- Curculigoside facilitates fear extinction and prevents depression-like behaviors in a mouse learned helplessness model through increasing hippocampal BDNF.Acta pharmacologica Sinica · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triptolide (TP), one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, and 2, 4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of tetrahydrobiopterin (BH4) synthesis, have been reported to have potent anti-inflammatory and immunosuppressive properties. However, the protective effects of TP and DAHP on cerebral ischemia have not been reported yet. In this study, we investigated the neuroprotective effects of TP and DAHP in a middle cerebral artery occlusion (MCAO) rat model. Furthermore, we examined whether the neuroprotective effects of TP and DAHP were associated with the inhibition of apoptosis through suppressing BH4 and inducible NOS (iNOS) synthesis or the activation of the phosphoinositide-3-kinase/serine-threonine kinase Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Our results showed that pretreatments with TP (0.2 mg/kg) and DAHP (0.5 g/kg) significantly reduced ischemic lesion volume, water content, and neuronal cell death compared with the vehicle MCAO rats. In addition, compared with the MCAO group, TP, and DAHP pretreatment groups significantly reduced astrocyte numbers, caspase-3, cleaved caspase-3, and NF-κB up-regulation, while increased Bcl-2 expression. Moreover, protein expressions of PI3K, Akt, and mTOR increased, while extracellular signal-regulated protein kinases 1 and 2 (ERK1 and ERK2) phosphorylation decreased in both the TP-treated rats and DAHP-treated rats. These results demonstrate that TP and DAHP can decrease cell apoptosis in focal cerebral ischemia rat brains and that the mechanism may be related to the activation of the PI3K/Akt/mTOR pathway and inactivation of the ERK1/2 pathway. Thus our hypothesis was reached PI3K/Akt/mTOR and ERK1/2 pathways may provide distinct cellular targets for a new generation of therapeutic agents for the treatment of stroke, and TP and DAHP may be potential neuroprotective agents for cerebral ischemia/reperfusion injury.
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