ArticleActa pharmacologica Sinica2023
Dl-3-n-butylphthalide promotes angiogenesis in ischemic stroke mice through upregulating autocrine and paracrine sonic hedgehog.
Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Efficacy and safety of anisodine hydrobromide injection in acute ischemic stroke-a multicenter real-world observational study.Frontiers in pharmacology · 2026Trial
- Efficacy and safety of DL-3-N-butylphthalide in the treatment of ischemic poststroke aphasia: A randomized clinical trial.Annals of clinical and translational neurology · 2024Trial
- Butylphthalide enhances neurorestoration following ischemic stroke by restructuring microvasculature through vimentin modulation.Journal of advanced research · 2026Article
- Effects of Antioxidant DI-3-N-Butylphthalide on Hemorrhagic Transformation Assessed by Propensity Score Matching in a Real-World Thrombolyzed Ischemic Stroke Patient Setting.Translational stroke research · 2026Article
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Decoding monocyte signatures in ischemic stroke: A multi-scale transcriptomic approach.Neural regeneration research · 2026Article
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- Electroacupuncture (EA) promotes angiogenesis and ameliorates dysregulated autophagy in ischemic stroke mice by modulating the ELAVL1/SIRT1/FOXO1 pathway.Metabolic brain disease · 2026Article
- Sevoflurane ameliorates cerebral ischemia-reperfusion injury by modulating mitochondrial dynamics and attenuating apoptosis via Shh-YAP1 signaling pathway.Molecular brain · 2026Article
- Endothelial cells secrete small extracellular vesicles to promote neuron endoplasmic reticulum stress injury via miR-146a-5p/Eif4g2 axis in ischemic stroke.Journal of advanced research · 2026Article
- Sodium oligomannate reduces cerebral infarction and improves neurological function through microbiota remodeling in MCAO/R rats.Frontiers in pharmacology · 2026Article
- Adjuvant neuroprotective therapies for acute ischemic stroke in the reperfusion era: a comparative narrative review of clinical evidence for edaravone, edaravone-dexborneol, and butylphthalide.Frontiers in neurology · 2026Review
- Identification and validation of microglia-associated genes in ischemic stroke using single-cell and bulk RNA-seq.Molecular brain · 2025Article
- Dl-3-n-Butylphthalide Promotes Cortical Angiogenesis via Akt/GSK-3β Signaling in Ischemic Stroke Mice.CNS neuroscience & therapeutics · 2025Article
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Dl-3-n-Butylphthalide Promotes Neurogenesis in Ischemic Stroke Mice Through Wnt/β-Catenin Signaling Activation and Neurotrophic Factor Production.Molecular neurobiology · 2025Article
- Celery seed derived reconstituted lipid nanoparticles as an innate neuron-targeted neuroprotective nanomedicine for ischemic stroke treatment.Journal of nanobiotechnology · 2025Article
- Dl-3-n-butylphthalide ameliorates diabetic foot ulcer by inhibiting apoptosis and promoting angiogenesis.World journal of diabetes · 2025Article
- LncRNA-mRNA co-expression network in the mechanism of butylphthalide treatment for ischemic stroke.BMC neurology · 2025Article
- Influence of diabetes on the efficacy of DL-3-n-butylphthalide in post-stroke cognitive impairment: a 12-month prospective cohort study.Frontiers in aging neuroscience · 2025Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dl-3-n-butylphthalide (NBP) is a small-molecule drug used in the treatment of ischemic stroke in China, which is proven to ameliorate the symptoms of ischemic stroke and improve the prognosis of patients. Previous studies have shown that NBP accelerates recovery after stroke by promoting angiogenesis. In this study, we investigated the mechanisms underlying the angiogenesis-promoting effects of NBP in ischemic stroke models in vitro and in vivo. OGD/R model was established in human umbilical vein endothelial cells (HUVECs) and human brain microvascular endothelial cells (HBMECs), while the tMCAO model was established in mice. The cells were pretreated with NBP (10, 50, 100 µM); the mice were administered NBP (4, 8 mg/kg, i.v.) twice after tMCAO. We showed that NBP treatment significantly stimulated angiogenesis by inducing massive production of angiogenic growth factors VEGFA and CD31 in both in vitro and in vivo models of ischemic stroke. NBP also increased the tubule formation rate and migration capability of HUVECs in vitro. By conducting the weighted gene co-expression network analysis, we found that these effects were achieved by upregulating the expression of a hedgehog signaling pathway. We demonstrated that NBP treatment not only changed the levels of regulators of the hedgehog signaling pathway but also activated the transcription factor Gli1. The pro-angiogenesis effect of NBP was abolished when the hedgehog signaling pathway was inhibited by GDC-0449 in HUVECs, by Sonic Hedgehog(Shh) knockdown in HUVECs, or by intracerebroventricular injection of AAV-shRNA(shh)-CMV in tMCAO mice. Furthermore, we found that HUVECs produced a pro-angiogenic response not only to autocrine Shh, but also to paracrine Shh secreted by astrocytes. Together, we demonstrate that NBP promotes angiogenesis via upregulating the hedgehog signaling pathway. Our results provide an experimental basis for the clinical use of NBP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.