DL‐3‐n‐butylphthalide suppressed autophagy and promoted angiogenesis in rats with vascular dementia by activating the Shh/Ptch1 signaling pathway

Niu, Xiaoli; Li, Meixi; Gao, Yaran; Xu, Guodong; Dong, Xiaoli; Chu, Bao; Lv, Peiyuan

doi:10.1016/j.neulet.2021.136266

Cited by 11 publications

(6 citation statements)

References 37 publications

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“…Previous reports have identified that NBP has extensive pharmacological effects in nervous system diseases (14)(15)(16). While a limited number of studies have shown that NBP has cardioprotective effects, the precise mechanisms are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…NBP was approved by the State Food and Drug Administration of China for the treatment of acute ischemic stroke in 2002. Previous studies have shown that NBP has various neuroprotective effects, such as improving mitochondrial function and anti-oxidative stress, inhibiting apoptosis and inflammation, regulating autophagy, improving microcirculation, and promoting neuron regeneration (14)(15)(16). In recent studies, NBP has been shown to exert cardioprotective effects on cardiac ischemic injury or IRI by inhibiting oxidative stress, affecting mitochondrial apoptosis, and regulating mitochondrial biogenesis (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

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Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

Zhang¹,

Zheng²,

Fu³

et al. 2022

J Thorac Dis

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Background: Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide.Undesirable myocardial damage may occur during reperfusion of the ischemic myocardium, and this is known as "ischemic reperfusion injury" (IRI). Currently, there are few effective drugs to alleviate IRI. Dl-3-n-butylphthalide (NBP) is recommended for the treatment of acute ischemic stroke in China. This study investigated the effects of NBP on IRI and its underlying mechanisms. Methods:The left anterior descending (LAD) coronary arteries of rats were occluded for 30 minutes and reperfused for 6 hours to establish the ischemia/reperfusion (I/R) model. NBP was administered intraperitoneally 2 hours before modeling and immediately after reperfusion. At 6 hours after reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining, enzyme-linked immunosorbent assay (ELISA), oxidative stress index, myocardial injury index, hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot analyses were performed to investigate the protective effects of NBP against IRI.Results: In the rat I/R model, NBP remarkably reduced the myocardial infarct size, alleviated myocardial injury and oxidative stress, improved the pathological alteration of cardiomyocytes and mitochondria, and upregulated mitophagy. In addition, the study demonstrated that the protective effects of NBP against IRI involved mitophagy mediated by the PTEN-induced putative kinase protein-1 (PINK1)/Parkin signaling pathway.Conclusions: NBP was able to protect the myocardium from IRI in rats through inhibiting oxidative stress and activating mitophagy, mediated by the PINK1/Parkin pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

Zhang¹,

Zheng²,

Fu³

et al. 2022

J Thorac Dis

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“…Therefore, the early control of BBB injury is important for subsequent white matter and neuronal protection. DL-3-n-butylphthalide has been validated for cognitive function improvement in many animal models of CCH [31][32][33][34][35][36][37][38], but most of the existing studies focus on its direct protective effects on neurons [34,[36][37][38], as well as its mechanisms in promoting angiogenesis [31,38], inhibiting neuroin ammation [32,33], and reducing reactive astrocyte proliferation [33,38], while the number of studies about BBB is very limited. In this experiment, we paid more attention to the changes in BBB permeability after CCH, and used EB leakage to re ect the degree of BBB destruction.…”

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. 2022

Preprint

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Vascular cognitive impairment (VCI) have been one of the main type of cognitive impairment. Chronic cerebral hypoperfusion (CCH) is the main cause of VCI. Blood-brain barrier damage plays an essential part in the pathogenesis of CCH induced cognitive impairment. At present, the treatment to VCI mainly focused on prevention, there is no drug clinically approved for the treatment of VCI. This study investigated the effects of DL-3-n-butylphthalide (NBP) on cognitive function and blood-brain barrier in chronic cerebral hypoperfusion rats. A modified bilateral common carotid artery occlusion (mBCCAO) model was applied to imitate chronic cerebral hypoperfusion. The feasibility of the model was verified by laser Doppler, 13N-Ammonia-Positron Emission Computed Tomography (PET) and Morris Water Maze. Subsequently, Morris water maze experiment to evaluate the effect of different doses of NBP (40mg/kg, 80mg/kg) on the improvement of cognitive impairment induced by mBCCAO. Evans blue staining and western blot of tight junction protein were conducted to explore the effect of NBP on the blood-brain barrier protection. At the same time, the changes of pericyte coverage in mBCCAO model and the effect of NBP on pericyte coverage were preliminarily explored. We found that, mBCCAO surgery led to obvious cognitive impairment and decreased whole cerebral blood flow in rats, among which the blood flow in cortex, hippocampus and thalamus brain regions decreased more significantly. High-dose NBP (80 mg/kg) improved long-term cognitive function in mBCCAO rats, alleviates Evans blue leakage and reduces 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.

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“…It has a certain vasodilatory effect, can effectively regulate the blood circulation status of the cardiovascular and cerebrovascular systems, increases the blood flow of the cerebral blood supply arteries, and regulates mitochondrial function. [4][5][6] However, butylphthalide has a relatively single target, and individual treatment effects for patients with vascular dementia vary greatly. [6,7] Some patients may show poor results after receiving only butylphthalide treatment.…”

Section: Introductionmentioning

confidence: 99%

Effect of butylphthalide combined with idebenone on vascular dementia: A retrospective observational analysis

Zhang,

Wu,

et al. 2024

Medicine

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To explore the efficacy and safety of butylphthalide combined with idebenone in the treatment of vascular dementia. The clinical data of 126 patients with vascular dementia who were admitted to our hospital between March 2021 and February 2023 were retrospectively reviewed. Among them, 62 patients received butylphthalide alone (single group) and 64 patients received butylphthalide combined with idebenone (combined group). Cognitive function scores, serum inflammatory factor levels, oxidative stress index levels, and incidence of adverse reactions were compared between the 2 groups before and after treatment. After treatment, the Hasegawa Dementia Scale, Mini Mental State Examination Scale, and activities of daily living scores in both groups were higher than before treatment, and the scores in the combined group were higher than before treatment (P < .05). After treatment, the levels of serum C-reactive protein, tumor necrosis factor-α, and interleukin 6 in both groups were lower than those before treatment, and those in the combined group were lower than those in the simple group (P < .05). After treatment, the levels of serum glutathione peroxidase and superoxide dismutase in the 2 groups were higher than those before treatment, and the level of malondialdehyde was lower than that before treatment. The levels of serum glutathione peroxidase and superoxide dismutase in the combined group were higher than those in the simple group, and the level of malondialdehyde was lower than that in the simple group (P < .05). There was no significant difference in the incidence of adverse reactions between the combined group (6.25%) and the simple group (3.23%) (P > .05). Compared with butylphthalide alone, intervention of butylphthalide combined with idebenone on vascular dementia can effectively reduce the degree of inflammatory and oxidative stress reactions, improve cognitive function, and promote the ability to perform activities of daily living in a safe manner.

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DL‐3‐n‐butylphthalide suppressed autophagy and promoted angiogenesis in rats with vascular dementia by activating the Shh/Ptch1 signaling pathway

Cited by 11 publications

References 37 publications

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

Effects of Dl-3-n-butylphthalide on Cognitive Functions and Blood-brain Barrier in Chronic Cerebral Hypoperfusion Rats

Effect of butylphthalide combined with idebenone on vascular dementia: A retrospective observational analysis

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