Effects of N-butylphthalide on the activation of Keap1/Nrf-2 signal pathway in rats after carbon monoxide poisoning

Li, Qin; Cheng, Yongmei; Bi, Minghong; Lin, Hongyang; Chen, Yufei; Zou, Yong; Liu, Yuanyuan; Kang, Hai; Guo, Yunliang

doi:10.1016/j.etap.2015.05.009

Cited by 24 publications

(24 citation statements)

References 25 publications

(19 reference statements)

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“…Afterward, rats were assigned into three groups as follows using a random number table: a normal control group (NC group, n = 48), a CO poisoning group (CO group, n = 48), and a NBP treatment group (NBP+CO group, n = 48). Rats both in CO group and NBP+CO group were exposed to 1000 ppm CO in air for 40 min and then to 3000 ppm for another 20 min in an animal oxygen chamber as described previously (Li Q. et al, 2015), while those in NC group were permitted to breathe fresh air. Carboxyhemoglobin (HbCO) concentration of arterial blood was detected after intraperitoneal injection 3% pentobarbital by a Blood Gas Analyzer (RapidLab, Bayer HealthCare, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study indicated that the significantly ultrastructural alterations occurred in brain parenchyma in rats after CO exposure, including brain edema, chromatin condensation, nucleus membrane and cell organelles decomposition, even neuronal death (Li Q. et al, 2015; Li et al, 2016). N -butylphthalide (NBP), a new drug extracted from celery seeds (see Figure 1 ), was approved by China Food and Drug Administration in 2002.…”

Section: Introductionmentioning

confidence: 99%

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N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

Zhang

Guo

et al. 2016

Front. Pharmacol.

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Carbon monoxide (CO) poisoning is one of the most important health concerns and may result in neuropathologic changes and neurologic sequelae. However, few studies have addressed the correlation between CO poisoning and blood–brain barrier (BBB) impairment. In this study, we investigated the effects of N-butylphthalide (NBP) on the expressions of zonula occludens-1 (ZO-1), claudin-5 and aquaporin-4 (AQP-4) proteins in a CO poisoning rat model. The results indicated that the brain water content was obviously increased, and the tight junctions between endothelial cells were disrupted, resulting in significant cerebral edema and BBB dysfunction in a rat model of CO poisoning. Meanwhile, the ultrastructure of endothelial cells and pericytes was seriously damaged, and the expressions of ZO-1 and claudin-5 were decreased at an early stage (<7 days). NBP treatment could efficiently maintain the ultrastructural and functional integrity of BBB, alleviate cerebral edema. Besides, NBP could also markedly increase the levels of both ZO-1 and claudin-5 proteins compared with those in rats exposed to CO (P < 0.05), whereas NBP had no apparent regulatory effect on AQP-4 expression. Taken together, this study highlights the importance of ZO-1 and claudin-5 proteins in maintaining BBB ultrastructure and function after CO poisoning. NBP, as a novel treatment approach, may effectively inhibit the down-regulation of ZO-1 and claudin-5 proteins (but not AQP-4), thereby preserving the barrier function and reducing cerebral edema after CO poisoning.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

Zhang

Guo

et al. 2016

Front. Pharmacol.

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“…[13] In addition, previous study has shown that butylphthalide has a neuroprotective effect in rats after acute CO poisoning. [14] We speculated that a combined therapy of MSC transplantation and butylphthalide might have a promising treatment outcome for DEACMP.…”

Section: Introductionmentioning

confidence: 99%

Combination of butylphthalide with umbilical mesenchymal stem cells for the treatment of delayed encephalopathy after carbon monoxide poisoning

Wang¹,

Li²,

Wu³

et al. 2016

Medicine

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Delayed encephalopathy after carbon monoxide (CO) poisoning (DEACMP) is still a clinical challenge. This study aimed to investigate the efficacy of combined therapy of mesenchymal stem cell (MSC) transplantation and butylphthalide in DEACMP patients.Forty-two DEACMP patients were treated with 1 of the 3 therapies: combined therapy of MSC transplantation and butylphthalide; MSC transplantation alone; or hyperbaric oxygen therapy. The MSCs were alternatively injected into the subarachnoid space and the carotid artery using a self-made high-pressure injector. The Mini-Mental State Examination and the Barthel index of activities of daily living were administered before the treatment, and at 1 month, 3 months, and 6 months after the treatment. Computed tomography and magnetic resonance imaging results before and after the treatment were compared.At 1 month, 3 months, and 6 months after the treatment, the Mini-Mental State Examination scores and the Barthl scores were significantly higher in patients with the combined therapy of MSC transplantation and butylphthalide than those in patients with MSC transplantation alone or hyperbaric oxygen therapy (all P < 0.0001). No significant adverse events occurred.The combination of MSC transplantation and butylphthalide is safe and effective in treating DEACMP.

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“…The main active component of NBP is dl-3-N-butylphthalide,which was originally isolated from celery seeds.NBP is a lipid-soluble drug with good blood-brain barrier permeability [11] .In animal models of cerebral apoplexy,NBP was mainly used for inhibiting platelet aggregation,reducing thrombosis,improving microcirculation,reducing the volume of cerebral infarction,resisting oxidative stress,protecting mitochondrial function,reducing neuronal apoptosis,alleviating inflammatory reaction,mediating autophagy of nerve cells,promoting neurogenesis and targeting in several pathophysiological mechanisms,which are mainly reflected in its obvious neuroprotective effect [12][13][14][15][16][17][18][19][20][21][22] .NBP are the only new drug to cure cerebral arterial thrombosis in cerebrovascular disease and was approved by China Food and Drug Administration (CFDA) in 2002.Therefore,NBP became the third original new drug with proprietary intellectual property rights in China after artemisinin and bicyclol.It was listed as one of recommended drugs in Guideline for Prevention of Cerebral Apoplexy in China in 2010 and 2014 and then NBP injection was successfully apporved to be listed in 2018 and soon became an important adjunct to the first-line treatment of cerebral artery thrombosis in China.After further studies on its application,it was found that the beneficial effects of NBP are beyond those of apoplexy.Especially in neurodegenerative disease fields,it was found that NBP and its ramifications have unique function and effects in AD,vascular dementia (VaD),PD,ALS and DEACMP treatment [23][24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of DL-3 n-butylphthalide on psychiatric,behavioural and cognitive functions in delayed encephalopathy after acute carbon monoxide poisoning

Chen¹,

Yang²,

Li³

et al. 2020

Preprint

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Background The main hazards of carbon monoxide (CO) poisoning are its serious clinical effects,high incidence and mortality of toxicity.Acute brain injury and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are the most common neurological complications.CO poisoning can cause neurological,psychiatric,behavioural and cognitive disorders,including cortical blindness,parkinsonism,amnesia,personality changes,dementia,and mental disorders such as anxiety and depression.This study was performed to assess the efficacy of DL-3 n-butylphthalide (NBP) and dexamethasone (DXM) and hyperbaric oxygen (HBO) on psychiatric,behavioural and cognitive functions in DEACMP.Patients and methods A total of 179 patients with DEACMP were recruited and assigned to the combined-therapy group(receiving NBP and DXM 5 mg/day plus HBO therapy) or the control group (HBO therapy as monotherapy).The behavioural and cognitive functions in patients were evaluated by the Mini-Mental State Examination (MMSE),the Montreal cognitive assessment (MoCA) scale and the Barthel index of activities of daily living (ADL) after the treatment at 1 month,3 months,and 1 year respectively.The psychiatric changes in patients were evaluated by the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) after the treatment at 3 months and 1 year respectively.Results At 1 month,3 months and 1 year after the treatment,the MMSE,MoCA and ADL scores were all significantly higher in the combined therapy group than those in the control group.At 3 months and 1 year after the treatment,the HAMA and HAMD scores were all significantly lower in the combined therapy group than those in the control group.There were no significant alterations in blood glucose,blood lipids,or liver or kidney function during the whole treatment session.Some patients experienced loss of appetite,mild headache and minor skin irritations.However,these patients recovered by themselves and needed no additional medications or special treatment. Conclusion These results indicated that NBP and DXM combined with HBO for the treatment of DEACMP can significantly improve the psychiatric,behavioural and cognitive functions of patients and is very safe.

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Effects of N-butylphthalide on the activation of Keap1/Nrf-2 signal pathway in rats after carbon monoxide poisoning

Cited by 24 publications

References 25 publications

N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

Combination of butylphthalide with umbilical mesenchymal stem cells for the treatment of delayed encephalopathy after carbon monoxide poisoning

Efficacy of DL-3 n-butylphthalide on psychiatric,behavioural and cognitive functions in delayed encephalopathy after acute carbon monoxide poisoning

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