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

Che, Ping; Zhang, Juan; Yu, Mingqian; Tang, Ping; Wang, Yanhui; Lin, Aolei; Xu, Jing; Zhang, Nan

doi:10.1111/cns.14112

Cited by 12 publications

(3 citation statements)

References 60 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, VD's development and therapeutic effect can be predicted by evaluating and dynamically observing the changes in antioxidant molecules in VD patients. IL-1β is highly expressed in serum, frontal cortex and hippocampus of VD patients, which may play a signi cant role in the mechanism of neuroin ammation [31,32]. The results of ELISA in this study showed that compared with Group Sham, the SOD activity in the serum of rats in Group VD decreased.…”

Section: Immunohistochemical Resultsmentioning

confidence: 52%

Low-dose Esketamine promotes brain protection via the ERK/Nrf2 pathway in vascular dementia rats

Shi,

Guo,

et al. 2023

Preprint

View full text Add to dashboard Cite

Backdround : By establishing the rat model of vascular dementia and observing the effects of low-dose Esketamine on cognitive function and related mechanisms in rats with vascular dementia, providing a new idea for clinical drug treatment of Vascular dementia (VD). Methods 100 rats were randomly divided into five groups: sham operation group, vascular dementia group, Esketamine group, Esketamine + PD98059 group, and Esketamine + DMSO group. Except for the sham operation group, the other groups were established vascular dementia rat models by intraperitoneal injection of sodium nitroprusside to reduce blood pressure and bilateral common carotid artery occlusion/reperfusion. The Morris water maze test assessed rats' learning and memory ability. ELISA detected changes in SOD and IL-1β levels in rat serum; the levels of ERK, Nrf2, and p-ERK in the hippocampus were detected by western blotting; and the pathological changes in the hippocampus of rats in each group were detected by HE staining. Results The results showed that the escape latency of VD rats was significantly higher than that of Group Sham and Group VK. In contrast, the times of crossing the platform and the staying time distance of the target quadrant of VD rats were significantly lower than that of Group Sham and Group VK. Compared with the Group VD, the expression of ERK, p-ERK and Nrf2 in the hippocampus of Group VK increased, which improved brain injury, increased the level of serum antioxidant SOD and decreased the level of inflammatory factor IL-1β. Conclusion Low-dose ketamine can improve cognitive impairment and reduce the damage to the hippocampus in VD rats. Its protective effect is related to increasing BDNF levels, activating the ERK/Nrf2 pathway, increasing antioxidant substances in the body and inhibiting inflammatory factors.

show abstract

Section: Immunohistochemical Resultsmentioning

confidence: 52%

Low-dose Esketamine promotes brain protection via the ERK/Nrf2 pathway in vascular dementia rats

Shi,

Guo,

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Existing studies indicated that NBP may ameliorate the loss of TJ proteins through the downregulation of autophagy levels in human brain microvascular endothelial cells in the oxygen–glucose deprivation model (Wu et al 2020 ). The HIF-1α/MMP signaling pathway, which is related to the expression of tight junction proteins, has been reported to be suppressed by NBP in the BCAS model (Che et al 2023 ). Third, inflammatory markers might play a part in NBP’s positive effect on the cerebral endothelium, which needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dl-3-n-butylphthalide on cognitive functions and blood–brain barrier in chronic cerebral hypoperfusion rats

Chen

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Vascular cognitive impairment (VCI) has been one of the major types of cognitive impairment. Blood–brain barrier damage plays an essential part in the pathogenesis of VCI. At present, the treatment of VCI is mainly focused on prevention, with no drug clinically approved for the treatment of VCI. This study aimed to investigate the effects of DL-3-n-butylphthalide (NBP) on VCI rats. A modified bilateral common carotid artery occlusion (mBCCAO) model was applied to mimic VCI. The feasibility of the mBCCAO model was verified by laser Doppler, 13N-Ammonia-Positron Emission Computed Tomography (PET), and Morris Water Maze. Subsequently, the Morris water maze experiment, Evans blue staining, and western blot of tight junction protein were performed to evaluate the effect of different doses of NBP (40 mg/kg, 80 mg/kg) on the improvement of cognitive impairment and BBB disruption induced by mBCCAO. Immunofluorescence was employed to examine the changes in pericyte coverage in the mBCCAO model and the effect of NBP on pericyte coverage was preliminarily explored. mBCCAO surgery led to obvious cognitive impairment and the decrease of whole cerebral blood flow, among which the blood flow in the cortex, hippocampus and thalamus brain regions decreased more significantly. High-dose NBP (80 mg/kg) improved long-term cognitive function in mBCCAO rats, alleviated Evans blue leakage and reduced the loss of tight junction proteins (ZO-1, Claudin-5) in the early course of the disease, thereby exerting a protective effect on the blood–brain barrier. No significant changes in pericyte coverage were observed after mBCCAO. High-dose NBP improved cognitive function in mBCCAO rats. High-dose NBP protected the integrity of BBB by upregulating TJ protein expression, rather than regulating pericyte coverage ratio. NBP could be a potential drug for the treatment of VCI.

show abstract

“…In dementia, LTP is commonly inhibited; thus, stimulating or extending LTP may aid in restoring learning and memory functions ( Paoletti et al, 2013 ). In dementia subtypes such as AD and VaD, synapses display functional deficits, including reductions in synapse numbers, impaired dendritic spine morphology, and diminished neurotransmission capabilities ( Piscopo et al, 2022 ; Che et al, 2023 ).…”

Section: Pharmacological Effects Of Saponin Compoundsmentioning

confidence: 99%

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Li,

Hou,

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

ObjectiveThis study aims to elucidate the intervention effects of saponin components from Polygala tenuifolia Willd (Polygalaceae) on dementia, providing experimental evidence and new insights for the research and application of saponins in the field of dementia.Materials and MethodsThis review is based on a search of the PubMed, NCBI, and Google Scholar databases from their inception to 13 May 2024, using terms such as “P. tenuifolia,” “P. tenuifolia and saponins,” “toxicity,” “dementia,” “Alzheimer’s disease,” “Parkinson’s disease dementia,” and “vascular dementia.” The article summarizes the saponin components of P. tenuifolia, including tenuigenin, tenuifolin, polygalasaponins XXXII, and onjisaponin B, as well as the pathophysiological mechanisms of dementia. Importantly, it highlights the potential mechanisms by which the active components of P. tenuifolia prevent and treat diseases and relevant clinical studies.ResultsThe saponin components of P. tenuifolia can reduce β-amyloid accumulation, exhibit antioxidant effects, regulate neurotransmitters, improve synaptic function, possess anti-inflammatory properties, inhibit neuronal apoptosis, and modulate autophagy. Therefore, P. tenuifolia may play a role in the prevention and treatment of dementia.ConclusionThe saponin components of P. tenuifolia have shown certain therapeutic effects on dementia. They can prevent and treat dementia through various mechanisms.

show abstract

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

Cited by 12 publications

References 60 publications

Low-dose Esketamine promotes brain protection via the ERK/Nrf2 pathway in vascular dementia rats

Low-dose Esketamine promotes brain protection via the ERK/Nrf2 pathway in vascular dementia rats

Effects of Dl-3-n-butylphthalide on cognitive functions and blood–brain barrier in chronic cerebral hypoperfusion rats

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Contact Info

Product

Resources

About