Improvement of cerebral ischemia–reperfusion injury by l-3-n-butylphthalide through promoting angiogenesis

Huang, Ying; Pan, Lishou; Wu, Ting

doi:10.1007/s00221-020-05978-6

Cited by 14 publications

(9 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[30][31][32] The recovery of brain function after CIRI is largely dependent on the restoration of blood flow through angiogenesis. 33 Therefore, improving the function of cerebrovascular injury is of great significance for the treatment of CIRI. Stem cells are able to secrete exosomes carrying various bioactive molecules to mediate stem cell function.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have found that stem cell‐derived exosomes are involved in I/R injury and the pathophysiological process has potential therapeutic value 30–32 . The recovery of brain function after CIRI is largely dependent on the restoration of blood flow through angiogenesis 33 . Therefore, improving the function of cerebrovascular injury is of great significance for the treatment of CIRI.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Human umbilical cord mesenchymal stem cells‐derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia–reperfusion injury by regulating miR‐320/KLF5 axis

Feng

Xia

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

Accumulating evidence suggests that human umbilical cord mesenchymal stem cell‐derived exosomes (hUC‐MSCs‐Exos) are a promising therapeutic strategy for cerebral ischemia–reperfusion injury (CIRI). However, the underlying mechanism remains unclear. hUC‐MSCs‐Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia/reoxygenation (H/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC‐MSCs‐Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT‐qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull‐down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR‐320, and KLF5. Ischemia–reperfusion (I/R) rat model was established for in vivo experiments. hUC‐MSCs‐Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR‐320 in H/R‐treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC‐MSCs‐Exos reversed the promoting effects of hUC‐MSCs‐Exos on cell viability, migration, and tube formation in H/R‐treated HBMECs in vitro and also abolished the protective effects of hUC‐MSCs‐Exos on cerebrovascular injury in I/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR‐320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR‐320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H/R‐treated HBMECs by upregulating KLF5. hUC‐MSCs‐Exos‐derived circDLGAP4 reduced cerebrovascular injury by regulating miR‐320/KLF5 signaling. These results provide a stem cell‐based approach to treat CIRI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cells‐derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia–reperfusion injury by regulating miR‐320/KLF5 axis

Feng

Xia

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…A previous study claimed that NBP protected BBB integrity and attenuated brain injury in the acute phase of ischemic stroke by decreasing MMP‐9 enzyme activity 54 . In addition, it was demonstrated that NBP promoted angiogenesis and cognitive function in chronic hypoxia and hypoperfusion model mice by mediating the HIF‐1α signaling pathway 55,56 . Taken together, we suggested that NBP may inhibit BBB leakage and inflammation by inhibiting the HIF‐1α/MMP signaling pathway in mice subjected to BCAS.…”

Section: Discussionmentioning

confidence: 60%

“…54 In addition, it was demonstrated that NBP promoted angiogenesis and cognitive function in chronic hypoxia and hypoperfusion model mice by mediating the HIF-1α signaling pathway. 55,56 Taken together, we suggested that NBP may inhibit BBB leakage and inflammation by inhibiting the HIF-1α/MMP signaling pathway in mice subjected to BCAS.…”

Section: Discussionmentioning

confidence: 73%

Dl‐3‐n‐butylphthalide promotes synaptic plasticity by activating the Akt/ERK signaling pathway and reduces the blood–brain barrier leakage by inhibiting the HIF‐1α/MMP signaling pathway in vascular dementia model mice

Che

Zhang

et al. 2023

CNS Neurosci Ther

View full text Add to dashboard Cite

Aims DL‐3‐n‐butylphthalide (NBP) exerts beneficial effects on global cognitive functions, but the underlying molecular mechanisms are still poorly understood. The present study aimed to investigate whether NBP mediates synaptic plasticity and blood–brain barrier (BBB) function, which play a pivotal role in the pathogenesis of vascular dementia (VaD), in a mouse model of bilateral common carotid artery stenosis (BCAS). Methods NBP was administered to model mice at a dose of 80 mg/kg by gavage for 28 days after surgery. Cognitive function was evaluated by behavioral tests, and hippocampal synaptic plasticity was evaluated by in vivo electrophysiological recording. Cerebral blood flow (CBF), hippocampal volume, and white matter integrity were measured with laser speckle imaging (LSI) and MRI. In addition, BBB leakage and the expression of proteins related to the Akt/ERK and HIF‐1α/MMP signaling pathways were assessed by biochemical assays. Results NBP treatment alleviated cognitive impairment, hippocampal atrophy, and synaptic plasticity impairment induced by BCAS. In addition, NBP treatment increased CBF, promoted white matter integrity, and decreased BBB leakage. Regarding the molecular mechanisms, in mice with BCAS, NBP may activate the Akt/ERK signaling pathway, which upregulates the expression of synapse‐associated proteins, and it may also inhibit the HIF‐1α/MMP signaling pathway, thereby increasing the expression of tight junction (TJ) proteins. Conclusion In conclusion, our results demonstrated the therapeutic effects of NBP in improving cognitive function via a wide range of targets in mice subjected to BCAS.

show abstract

“…It could be a potential biomarker for the treatment of ischemic stroke [ 74 , 75 ]. Butylphthalide has been found to improve the prognosis of ischemic stroke via regulation of Nrf2 [ 76 ]. Due to the interaction between oxidative stress and inflammatory response, detection and interventions of inflammatory reaction could have positive significance for the treatment of ischemic stroke.…”

Section: Pathophysiological Mechanisms Of Ischemic Strokementioning

confidence: 99%

Oxidative Injury in Ischemic Stroke: A Focus on NADPH Oxidase 4

Ye²,

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Ischemic stroke is a leading cause of disability and mortality worldwide. Thus, it is urgent to explore its pathophysiological mechanisms and find new therapeutic strategies for its successful treatment. The relationship between oxidative stress and ischemic stroke is increasingly appreciated and attracting considerable attention. ROS serves as a source of oxidative stress. It is a byproduct of mitochondrial metabolism but primarily a functional product of NADPH oxidases (NOX) family members. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is most closely related to the formation of ROS during ischemic stroke. Its expression is significantly upregulated after cerebral ischemia, making it a promising target for treating ischemic stroke. Several drugs targeting NOX4, such as SCM-198, Iso, G-Rb1, betulinic acid, and electroacupuncture, have shown efficacy as treatments of ischemic stroke. MTfp-NOX4 POC provides a novel insight for the treatment of stroke. Combinations of these therapies also provide new approaches for the therapy of ischemic stroke. In this review, we summarize the subcellular location, expression, and pathophysiological mechanisms of NOX4 in the occurrence and development of ischemic stroke. We also discuss the therapeutic strategies and related regulatory mechanisms for treating ischemic stroke. We further comment on the shortcomings of current NOX4-targeted therapy studies and the direction for improvement.

show abstract

Improvement of cerebral ischemia–reperfusion injury by l-3-n-butylphthalide through promoting angiogenesis

Cited by 14 publications

References 45 publications

Human umbilical cord mesenchymal stem cells‐derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia–reperfusion injury by regulating miR‐320/KLF5 axis

Human umbilical cord mesenchymal stem cells‐derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia–reperfusion injury by regulating miR‐320/KLF5 axis

Dl‐3‐n‐butylphthalide promotes synaptic plasticity by activating the Akt/ERK signaling pathway and reduces the blood–brain barrier leakage by inhibiting the HIF‐1α/MMP signaling pathway in vascular dementia model mice

Oxidative Injury in Ischemic Stroke: A Focus on NADPH Oxidase 4

Contact Info

Product

Resources

About