benzofurans and Nervous-System-Diseases

The 3-N-butylphthalide (NBP) comprises one of the chemical constituents of celery oil. It has a series of pharmacologic mechanisms including reconstructing microcirculation, protecting mitochondrial function, inhibiting oxidative stress, inhibiting neuronal apoptosis, etc. Based on the complex multi-targets of pharmacologic mechanisms of NBP, the clinical application of NBP is increasing and more clinical researches and animal experiments are also focused on NBP. The aim of this review was to comprehensively and systematically summarize the application of NBP on neurologic diseases and briefly summarize its application to non-neurologic diseases. Moreover, recent progress in experimental models of NBP on animals was summarized.. Literature was collected from PubMed and Wangfang database until November 2018, using the search terms including "3-N-butylphthalide," "microcirculation," "mitochondria," "ischemic stroke," "Alzheimer disease," "vascular dementia," "Parkinson disease," "brain edema," "CO poisoning," "traumatic central nervous system injury," "autoimmune disease," "amyotrophic lateral sclerosis," "seizures," "diabetes," "diabetic cataract," and "atherosclerosis.". Literature was mainly derived from English articles or articles that could be obtained with English abstracts and partly derived from Chinese articles. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors' files.. NBP has become an important adjunct for ischemic stroke. In vascular dementia, the clinical application of NBP to treat severe cognitive dysfunction syndrome caused by the hypoperfusion of brain tissue during cerebrovascular disease is also increasing. Evidence also suggests that NBP has a therapeutic effect for neurodegenerative diseases. Many animal experiments have found that it can also improve symptoms in other neurologic diseases such as epilepsy, cerebral edema, and decreased cognitive function caused by severe acute carbon monoxide poisoning. Moreover, NBP has therapeutic effects for diabetes, diabetes-induced cataracts, and non-neurologic diseases such as atherosclerosis. Mechanistically, NBP mainly improves microcirculation and protects mitochondria. Its broad pharmacologic effects also include inhibiting oxidative stress, nerve cell apoptosis, inflammatory responses, and anti-platelet and anti-thrombotic effects.. The varied pharmacologic mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacologic effects await further study.

Topics: Animals; Benzofurans; Humans; Nervous System Diseases; Neuroprotective Agents; Oxidative Stress

The research of alternative treatment for ischemic stroke and degenerative diseases has always been a priority in neurology. 3-N-Butylphthalide (NBP), a family of compounds initially isolated from the seeds of

Topics: Apium; Apoptosis; Benzofurans; Humans; Inflammation; Nervous System Diseases; Neuroprotective Agents; Oxidative Stress; Plant Extracts

The discovery of enhancer regulation in the mesencephalon and the concept that it plays a key role in the operation of innate and acquired drives [Neurochem. Res. 28 (2003) 1187] sets the trace amines (TAs) in their true physiological perspective. The regulation is defined as the existence of enhancer-sensitive neurons in the brain capable of working in a split-second on a high activity level due to endogenous enhancer substances. For the time being, only beta-phenylethylamine (PEA) and tryptamine are the experimentally analyzed examples. (-)-Deprenyl (selegiline), widely used in Parkinson's disease and Alzheimer's disease today, and known as the first selective monoamine oxidase (MAO) type-B inhibitor for decades, was identified as a PEA-derived synthetic mesencephalic enhancer substance. An important and convincing confirmation of the enhancer concept was the recent development of a highly specific and potent tryptamine-derived synthetic mesencephalic enhancer substance, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP]. This substance, which is specific and hundreds of times more potent than selegiline, is now the best experimental tool to study the enhancer regulation in the mesencephalon and a promising candidate to significantly surpass the therapeutic efficiency of selegiline in depression, Parkinson's disease, and Alzheimer's disease.

Topics: Animals; Antidepressive Agents; Benzofurans; Humans; Mesencephalon; Nervous System Diseases; Neuroprotective Agents; Phenethylamines; Psychotropic Drugs; Selegiline; Tryptamines

Topics: Amiodarone; Angina Pectoris; Benzofurans; Cerebrospinal Fluid Proteins; Electromyography; Humans; Inclusion Bodies; Lipid Metabolism; Microscopy, Electron; Movement Disorders; Muscles; Nervous System Diseases; Paresthesia; Perhexiline; Peripheral Nerves; Peripheral Nervous System Diseases; Pigments, Biological; Piperidines; Polyradiculoneuropathy; Schwann Cells; Skin; Tremor

To investigate the effect of Butylphthalide and Xue Shuan Tong on serum inflammatory factors and prognosis of patients with cerebral infarction. One hundred and twenty patients with acute cerebral infarction were randomly divided into control group, Butylphthalide group and Xue Shuan Tong group, with 40 patients in each group. Conventional therapy was performed in the control group; On the basis of conventional therapy, 100ml Butylphthalide intravenously twice a day was administrated among patients in Butylphthalide group; On the basis of conventional therapy, 250ml 0.9% NaCl intravenously once a day was conducted among patients in Xue Shuan Tong group. A treatment course of continuous 7 days was taken in the three groups. The serum levels of IL-2 and CGRP were detected for patients in the three groups before and after treatment. Carotid plaque thickness and size as well as intima-media thickness were detected by ultrasonic testing for patients in three groups before treatment and 90 days after follow-up. The NIHSS, Barthel and MRS scoring were performed for all the patients after 90-day follow-up to evaluate the prognosis. After treatment, differences in the levels of IL-2 and CGRP for patients in the three groups showed statistical significance (P<0.05), while the levels of IL-2 and CGRP in Xue Shuan Tong group were significantly higher than those in the other two groups (P<0.05). After 7-day treatment, plaque size and thickness in Xue Shuan Tong group and Butylphthalide group were significantly reduced, compared with those before treatment (P<0.05), but no significant differences was shown in the plaque size and thickness between Xue Shuan Tong group and Butylphthalide group (P>0.05) .The CA-IMT in Xue Shuan Tong group and Butylphthalide group was significantly reduced after treatment, and that in Butylphthalide group was significantly larger than that in Xue Shuan Tong group (P<0.05). After 90-day follow-up, NIHSS scores in Butylphthalide group were significantly less than those in the other two groups (P<0.05). After 90-day follow-up, Barthel scores in Butylphthalide group and Xue Shuan Tong group were significantly larger than those in control group (P<0.05), while differences between Butylphthalide group and Xue Shuan Tong group indicated no statistical significance (P>0.05). There were significant differences in MRS scores among patients in the three groups after 90-day follow-up (P<0.05). Butylphthalide and Xue Shuan Tong are clinically effective

Topics: Aged; Aged, 80 and over; Benzofurans; Calcitonin Gene-Related Peptide; Carotid Arteries; Carotid Intima-Media Thickness; Cerebral Infarction; Drugs, Chinese Herbal; Female; Humans; Inflammation; Interleukin-2; Male; Middle Aged; Nervous System Diseases; Plaque, Atherosclerotic; Prognosis

The butylphthalide(NBP), a colorless or light yellow viscous oily component isolated from celery seeds, has the effects of anti-inflammation, anti-oxidative stress, protecting blood-brain barrier, improving cerebral microcirculation, and promoting angiogenesis. It can protect the neurological function of patients with ischemic stroke through a variety of mechanisms, improve the symptoms of patients, and contribute to the long-term recovery of them. Therefore, independently developed in China, NBP was approved by State Food and Drug Administration for the clinical treatment of stroke patients in 2002. At the same time, owing to the complex multi-target pharmacological mechanism, NBP has been frequently used in clinical practice. As frequently verified, it has obvious effects in the treatment of other neurological diseases such as Alzheimer's disease, vascular dementia, Parkinson's disease, autoimmune diseases, depression, traumatic central nervous system injury. Moreover, it demonstrates significant pharmacological effects on non-neurological diseases such as diabetes mellitus and myocardial infarction. Therefore, this study summarizes the research progress on roles of NBP in nervous system diseases and non-nervous system diseases, and the pharmacological characteristics and mechanisms of NBP, which is expected to lay a basis for research on related targets.

Topics: Benzofurans; Humans; Nervous System Diseases; Neuroprotective Agents; Oxidative Stress

Cerebral stroke occurs following ischemic and hemorrhagic lesions in the brain. Survival and recovery of stroke patients depend on the severity of the initial injury but also the therapeutic approaches applied for emergent lifesaving and continuing post-stroke management. Dl-3-n-Butylphthalide (NBP), an active compound derived from Chinese celery seeds, has shown clinical efficacy in the treatment of ischemic cerebral stroke.. In the present study we explored the therapeutic effect of NBP in a rat model of intracerebral hemorrhage (ICH), focusing on its potential role in promoting neovascularization in the perihemorrhagic zone. ICH was induced in male Sprague-Dawley rats by unilateral injection of autologous blood into the globus pallidus, with sham-operated (Sham group), vehicle-treated (ICH) and NBP-treated (at 10 and 25 mg/kg/Bid, p.o., ICH + NBP10 and ICH + NBP25, respectively) groups examined behaviorally, macroscopically, histologically and biochemically at 1, 3, 7 and 15 days (d) post operation. Rats in the ICH + NBP10 and ICH + NBP25 groups showed reduced Longa's motor scores relative to the ICH groups at the 3 and 7d time points, while the hematoma volume was comparable in the two NBP relative to the ICH groups as measured at 7d and 15d. In the perihemorrhagic zone, the numeric density of blood vessels immunolabeled by CD34, an angiogenic marker, was greater in the ICH + NBP10 and ICH + NBP25 than ICH groups, more so in the higher dosage group, at 1, 3, 7 and 15d. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins-2 (Ang-2) proteins were elevated in the NBP groups relative to the sham and vehicle controls in immunoblotting of tissue lysates from the injection region.. These results suggest that NBP can alleviate neurological defects following experimentally induced local brain hemorrhage, which is associated with a potential role of this drug in promoting neovascularization surrounding the bleeding loci.

Topics: Animals; Benzofurans; Brain; Cerebral Hemorrhage; Disease Models, Animal; Male; Nervous System Diseases; Rats, Sprague-Dawley; Stroke; Vascular Endothelial Growth Factor A

Postoperative neurological deficits impair the overall outcome of revascularization surgery for patients with moyamoya disease (MMD). dl-3-n-butylphthalide (NBP) is approved for the treatment of ischemic stroke in China. This pilot study evaluated the effect of NBP on perioperative stroke and neurological deficits in patients with MMD.. The authors studied cases in which patients underwent combined revascularization surgery for MMD at their institution, with or without NBP administration. The overall study group included 164 patients (213 surgically treated hemispheres), including 49 patients who received NBP (25 mg twice daily) for 7 postoperative days. The incidence of perioperative stroke and transient neurological deficit (TND) and the severity of neurological deficits were compared between 49 propensity score-matched case pairs with or without NBP treatment. Subgroup analyses by type of onset and preoperative neurological status were also performed to determine specific characteristics of patients who might benefit from NBP administration.. In the overall cohort, baseline characteristics differed with respect to preoperative stroke and modified Rankin Scale (mRS) score between patients who received NBP and those who did not receive it. In the 49 propensity score-matched pairs, postoperative stroke was observed in 11 patients and TND occurred in 21 patients, with no significant difference in incidence between the 2 groups. However, the TND was less severe in the NBP-treated group (p = 0.01). At 1 month after surgery, the neurological outcome was more favorable (p = 0.001) and the disability-free recovery rate was higher in patients with NBP treatment (p < 0.001). The number of patients who experienced an improved neurological function, compared to preoperative function, as measured by mRS, was greater in the NBP group than in the no-NBP group (p < 0.001). Multivariable analysis revealed that NBP administration was associated with decreased severity of TND (OR 0.28, p = 0.02), improved neurological function (OR 65.29, p = 0.04), and lower postoperative mRS score (OR 0.06, p < 0.001). These beneficial effects of NBP remained significant in ischemic type MMD and patients with preoperative mRS scores of 2 or greater.. Postoperative administration of NBP may alleviate perioperative neurological deficits after revascularization surgery for MMD, especially in patients with ischemic MMD and unfavorable preoperative status. The results of this study suggest that randomized controlled trials to assess the potential benefit of NBP in patients with MMD may be warranted.

Topics: Adult; Benzofurans; Cerebral Revascularization; Cohort Studies; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Moyamoya Disease; Nervous System Diseases; Neuroprotective Agents; Pilot Projects; Postoperative Complications; Propensity Score; Prospective Studies

Chronic constipation is very frequent in the general population. Although usually considered banal, this disorder has considerable personal, social and healthcare impact. Several studies have shown that the psychological impact exceeds that caused by rheumatoid arthritis or haemodialysis. Recently, prucalopride, a highly selective 5-HT4 receptor agonist has been shown to improve the symptoms of chronic constipation and to have a beneficial effect on social and healthcare impact. The drug was approved by the European Medicine Agency, in 2009 at a dose of 2 mg/day, 'for symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief'. Neurological side effects or psychiatric disorders have not been reported previously with prucalopride. We present the case of a 61-year-old woman, who developed such adverse effects when given prucalopride for the treatment for chronic constipation.. A few hours after oral administration of this drug at therapeutic dose (2 mg/day), the patient experienced life-threatening neurological effects that included visual hallucination, loss of balance and memory, disorientation, exhaustion and suicidal ideation. Analysis with the Naranjo algorithm indicated a 'possible' relationship between prucalopride and these disorders.. This is the first report of prucalopride-induced neurological side effects and psychiatric disorders with prucalopride. The absence of other similar reports suggests that prucalopride rarely causes these adverse effects.

Topics: Benzofurans; Chronic Disease; Constipation; Female; Hallucinations; Humans; Memory Disorders; Mental Disorders; Middle Aged; Nervous System Diseases; Orientation; Postural Balance; Serotonin; Serotonin 5-HT4 Receptor Agonists; Suicidal Ideation

A series of 12, N-(2-benzoylbenzofuran-3-yl)-3-(substituted)-propanamide analogs was designed and synthesized to meet the pharmacophore requirement essential for anticonvulsant activity. All the compounds were characterized by IR, (1)H NMR and mass spectral data followed by their anticonvulsant evaluation according to the Antiepileptic Drug Development Program (ADD) protocol. The present study has proved the hypothesis concerning the pharmacophore model with essential binding sites. N-(2-benzoylbenzofuran-3-yl)-3-(4-(2-fluorophenyl)piperazin-1-yl) propanamide, 6h was found to be the most active compound in both maximal electroshock seizure (MES) and subcutaneous metrazol (scMET) seizure test at 30 and100 mg/kg respectively at 0.5 and 4.0 h.

Topics: Animals; Anticonvulsants; Benzofurans; Convulsants; Drug Design; Electroshock; Indicators and Reagents; Mice; Nervous System Diseases; Pentylenetetrazole; Piperazines; Rats; Seizures

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

Topics: Analysis of Variance; Animals; Antioxidants; Benzofurans; Brain Infarction; Brain Injuries; Cerebral Cortex; Disease Models, Animal; Infarction, Middle Cerebral Artery; Magnetic Resonance Imaging; Male; Nervous System Diseases; Neurologic Examination; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tetrazolium Salts

Our previous studies showed that ligands to type 2 imidazoline receptors (I₂R), including 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) and Idazoxan, were effective in reducing spinal cord inflammation caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we determined the effective therapeutic time window of 2-BFI and found that administration of 2-BFI in mice before the appearance of ascending flaccid paralysis (1-10 days post immunization), but not during the period when neurological deficits occurred (11-20 days post immunization), significantly ameliorated EAE-induced neurobehavioral deficits, reduced the infiltration of inflammatory cells into the spinal cord, and reduced the level of demyelination. More interestingly, giving 2-BFI during 1-10 days post immunization selectively suppressed IL-17 levels in the peripheral blood, which strongly suggests that IL-17 may be a good early marker to indicate EAE progression and that 2-BFI may target CD4⁺ T lymphocytes, especially Th17 cells to reduce IL-17 expression. Collectively, these studies led us to envisage that 2-BFI can be a useful drug to treat multiple sclerosis (MS) when used in combination with an early indicator of MS progression, such as IL-17.

Topics: Analysis of Variance; Animals; Benzofurans; Calcium-Binding Proteins; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Freund's Adjuvant; Imidazoles; Indoles; Mice; Mice, Inbred C57BL; Microfilament Proteins; Myelin Sheath; Myelin-Oligodendrocyte Glycoprotein; Nervous System Diseases; Peptide Fragments; Spinal Cord Injuries; Time Factors

In 1979 approximately 2,000 people were exposed to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) due to ingestion of contaminated cooking oil in Taiwan. Although a previous study has shown delayed developmental milestones and poorer neurocognitive functioning in children born to exposed mothers, it is unclear whether neurocognitive functioning was impaired in people who were directly exposed to the PCBs and PDCFs.. The objective of this study was to compare neurocognitive functioning in people exposed to PCBs and PCDFs with that of unexposed sex- and age-matched neighbors.. We conducted a retrospective cohort study among exposed and unexposed subjects > or =60 years of age using prospective outcome measurements. We evaluated neurocognitive tests including cognition, memory modalities, learning, motor and sensory function, mood, and daily activity.. In total, 162 (59%) exposed and 151 (55%) reference subjects completed this study. In exposed men, all test results were similar to the reference group; however, exposed women had reduced functioning in attention and digit span (ADS), visual memory span (VMS), and verbal memory recalls (VMR), especially learning ability. We also found a borderline reduction in the Mini-Mental State Examination. The digit symbol, motor, sensory, depression (determined by the Geriatric Depression Scale-Short Form), and activity of daily life were not different between the exposed and reference groups. A significant dose-response relationship was found for VMR, ADS, and VMS.. Our study showed dose-dependent neurocognitive deficits in certain aspects of attention, visual memory, and learning ability in women previously exposed to PCBs and PCDFs, but not in exposed men.

Topics: Aged; Benzofurans; Cognition Disorders; Cohort Studies; Dibenzofurans, Polychlorinated; Environmental Exposure; Humans; Middle Aged; Nervous System Diseases; Neuropsychological Tests; Polychlorinated Biphenyls; Taiwan

Topics: Amiodarone; Benzofurans; Humans; Male; Middle Aged; Nervous System Diseases

Rats were treated with amiodarone (20 mg/kg/day) up to 6 weeks and the neurotoxicity was assessed by determining changes in motor coordination, pain-threshold and rectal temperature every week during treatment. Body weight gain was decreased during amiodarone treatment and it was significant at and after 5 weeks. Food intake and water consumption were significantly reduced during treatment. After the first week of treatment with amiodarone, rats showed decreased ability to balance on horizontal rods. In the hot plate test (paw-lick), the amiodarone treated rats showed increased pain-thresholds throughout the treatment. Hypothermia was significant only at 6 weeks. These results show that amiodarone causes toxicity in rats and this model might be useful for further studies. Decreased motor-coordination, and increased pain-responding times may indicate development of peripheral neuropathy in addition to muscle weakness.

Topics: Amiodarone; Animals; Benzofurans; Body Temperature; Body Weight; Drinking Behavior; Feeding Behavior; Male; Motor Skills; Nervous System Diseases; Pain; Rats; Rats, Inbred Strains

Rats and mice were given amiodarone by mouth at doses of 50 mg/kg/day. The drug induced accumulations of lipids within lysosomes, leading to the formation of cytoplasmic bodies. These were found in many tissues, both nervous and nonnervous, but were excluded from regions with blood-brain or blood-nerve barriers. Of nervous system regions lying outside a vascular barrier, autonomic ganglia were the most affected, with large accumulations of lysosomal bodies in nerve cells and processes, and evidence of degenerative changes. the myenteric plexus was also involved. No significant changes were seen in peripheral nerves. A limited period of increased permeability caused by nerve crush, or due to immaturity of the blood-nerve barrier resulted in the short-lived appearance of drug-induced inclusions. The rate of regeneration of axons following nerve crush was not affected, although there were small defects in myelination.

Topics: Amiodarone; Animals; Benzofurans; Mice; Mice, Inbred BALB C; Nervous System Diseases; Neurotoxins; Peripheral Nervous System Diseases; Rats; Rats, Inbred Strains

Fifty-four consecutive patients were treated with amiodarone for symptomatic ventricular tachycardia or ventricular fibrillation refractory to treatment with conventional antiarrhythmic drugs. A reversible neurologic syndrome of tremor, ataxia, and occasionally peripheral neuropathy without nystagmus, dizziness, encephalopathy, or long-tract signs developed in 54% of the patients and was the most common reason for altering or discontinuing drug therapy. Neurologic side effects improved or resolved within 2 days to 4 weeks of decreasing or discontinuing amiodarone. Frequent neurologic toxicity is a hitherto undescribed complication of amiodarone therapy. Wider recognition of this syndrome will avoid unnecessary and costly diagnostic evaluation.

Topics: Amiodarone; Ataxia; Benzofurans; Female; Humans; Male; Middle Aged; Nervous System Diseases; Tremor

Amiodarone, a drug used to treat refractory cardiac arrhythmias, produced a peripheral neuropathy in 5 of 50 cases (10%). Although the neuropathy may be severe, it tends to improve with lowering of the dosage or discontinuation of the medication.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Nervous System Diseases; Paresthesia; Peripheral Nervous System Diseases; Tremor

Topics: Amiodarone; Angina Pectoris; Benzofurans; Demyelinating Diseases; Humans; Male; Middle Aged; Nervous System Diseases