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1.
Bol. latinoam. Caribe plantas med. aromát ; 18(5): 459-479, sept. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1008268

RESUMO

Neuronal cell damage is often caused by prolonged misuse of Methylphenidate (MPH). Topiramate (TPM) carries neuroprotective properties but its assumed mechanism remains unclear. The present study evaluates in vivo role of various doses of TPM and its mechanism against MPH-induced motor activity and related behavior disorder. Thus, we used domoic acid (DOM), bicuculline (BIC), Ketamine (KET), Yohimibine (YOH) and Haloperidole (HAL) as AMPA/kainite, GABAA, NMDA, ɑ2 adrenergic and D2 of dopamine receptor antagonists respectively. Open Field Test (OFT), Elevated Plus Maze (EPM) and Forced Swim Test (FST) were used to study motor activity, anxiety and depression level. TPM (100 and 120 mg/kg) reduced MPH-induced rise and inhibited MPH-induced promotion in motor activity disturbance, anxiety and depression. Pretreatment of animals with KET, HAL, YOH and BIC inhibited TPM- improves anxiety and depression through the interacting with Dopaminergic, GABAA, NMDA and ɑ2-adrenergic receptors.


El daño a las células neuronales a menudo es causado por el uso prolongado de metilfenidato (MPH). El topiramato (TPM) tiene propiedades neuroprotectoras, pero su mecanismo de acción no es claro. El presente estudio evalúa el papel in vivo de varias dosis de TPM y su mecanismo contra la actividad motora inducida por MPH y el trastorno de comportamiento relacionado. Utilizamos ácido domoico (DOM), bicuculina (BIC), ketamina (KET), yohimbina (YOH) y haloperidol (HAL), así como antagonistas AMPA/kainato, GABAA, NMDA, ɑ2-adrenérgico y D2 dopaminérgicos, respectivamente. Se utilizaron las pruebas de campo abierto (OFT), elevación de laberinto (EPM) y natación forzada (FST) para estudiar la actividad motora, la ansiedad y el nivel de depresión. El TPM (100 y 120 mg/kg) redujo el aumento inducido por MPH e inhibió la promoción inducida por MPH en la alteración de la actividad motora, la ansiedad y la depresión. El tratamiento previo de animales con KET, HAL, YOH y BIC inhibió el TPM, mejora la ansiedad y la depresión a través de la interacción con los receptores dopaminérgicos, GABAA, NMDA y ɑ2-adrenérgico.


Assuntos
Animais , Masculino , Ratos , Comportamento Animal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , /farmacologia , Transtornos Mentais/prevenção & controle , Metilfenidato/efeitos adversos , Ratos Wistar , Neurotransmissores/metabolismo , Transtornos Mentais/induzido quimicamente , Atividade Motora/efeitos dos fármacos
2.
Adv Exp Med Biol ; 1155: 821-846, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468450

RESUMO

Lead (Pb2+) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb2+-induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb2+ has developmentally impacted higher order cognitive and behavioral systems. The present study evaluated the effects of developmental Pb2+-exposure (150 ppm lead acetate in the drinking water) in Long Evans Hooded rats through the Attention Set-Shift Test (ASST) between postnatal days (PND) 60-90. Treatment groups were comprised of Control (0 ppm), Perinatal (150 ppm), and Perinatal+Taurine (150 ppm + 0.05% Taurine in the drinking water) rats (N = 36; n = 6 per treatment group for each sex). Frontoexecutive functions were evaluated based on trials-to-criterion (TTC) and errors-to-criterion (ETC) measures for simple and complex discriminations (SD & CD), intradimensional and extradimensional shifts (ID & ED), as well as reversals (Rev) of the CD, I-, and ED stages, respectively. Post-testing, the prelimbic (PrL), infralimbic (IL), orbital ventral frontal (OV), orbital ventro-lateral (OVL), and hippocampal (HP) brain regions were extracted and processed through Liquid Chromatography/Mass Spectrophotometry (LC/MS) for determining the GABA and Taurine ratios relative to Glutamate, Dopamine, Norepinephrine, Epinephrine, and Serotonin. The ASST data revealed that Perinatal rats are negatively impacted by developmental Pb2+-exposures evidenced by increased TTC and ETC to learn the SD, ID, and ID-Rev with unique sex-based differences in frontoexecutive dysfunctions. Moreover, Perinatal+Taurine co-treated rats exhibited a recovery of the frontoexecutive dysfunctions observed in Perinatal rats to levels equivalent to Control rats across both sexes. The LC/MS data revealed altered brain sub-region specific patterns across the PrL, IL, OV, OVL, and HP in response to developmental Pb2+-exposure that produced an altered neurochemical signaling profile in a sex-dependent manner, which may underlie the observed frontoexecutive dysfunctions, cognitive inflexibility, and associated motivation deficits. When taurine co-treatment was administered concurrently for the duration of developmental Pb2+-exposure, the observed frontoexecutive dysfunctions were significantly reduced in both ASST task performance and neurochemical ratios that were comparable to Control levels for both sexes. Altogether, the data suggest that taurine co-treatment may facilitate neuroprotection, mitigate neurotransmitter excitability balancing, and perhaps ameliorate against neurotoxicant exposures in early development as a potential psychopharmacotherapy.


Assuntos
Atenção , Função Executiva , Chumbo/efeitos adversos , Exposição Materna/efeitos adversos , Taurina/farmacologia , Animais , Feminino , Aprendizagem , Masculino , Fármacos Neuroprotetores/farmacologia , Gravidez , Ratos , Ratos Long-Evans
3.
Adv Exp Med Biol ; 1155: 869-874, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468453

RESUMO

Our group previously reported that taurine has a protective capacity on the hippocampus and cerebellum of arsenic (As)-exposed mouse. In the present study, we explore whether taurine demonstrates protection against As toxicity in primary cortical neurons. Primary cortical neurons were exposed to various concentrations of arsenite and cell viability was assessed to confirm the toxicity of As on cortical neurons. The protection of taurine was examined after primary cortical neurons were treating with arsenite and taurine for 24 h. The cell viability was examined by MTT and caspase-3 activity assay. The expression of Bax and Bcl-2 was determined by western blot. The results showed that As exposure reduced cell viability and enhanced the activity of caspase-3, which were markedly inhibited by taurine treatment. The expression of Bax and Bcl-2 were disturbed by As exposure, which were reversed by taurine. These results indicated that taurine expose protective effect on As-exposed primary cortical neurons and its mechanism maybe involved the regulation of Bax/Bcl-2.


Assuntos
Arsênico/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Taurina/farmacologia , Animais , Apoptose , Sobrevivência Celular , Células Cultivadas , Camundongos , Neurônios/citologia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
4.
Life Sci ; 234: 116747, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408661

RESUMO

AIMS: The present study was aimed to investigate the neuroprotective effect of HSP70 against neuroinflammation in a rotenone-induced Parkinson's disease model. MATERIALS AND METHODS: In the present study, SH-SY5Y cells were treated with HSP70 (5-20 mg/L) for 72 h. Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), levels of oxidative markers, mitochondrial fragmentation, apoptosis, and mRNA and protein expressions of signal transducer and activator of transcription (STAT)-3 and nuclear factor-kappa B (NF-κB) were assessed. KEY FINDINGS: Cells treated with 5, 10, 15, and 20 mg/L of HSP70 exhibited increased, by 61.7%, 70.3%, 84.6%, and 96.7%, respectively, in cell viability. ROS and lipid peroxidation levels decreased following treatment with HSP70, and reductions in glutathione (GSH), catalase, glutathione peroxidase (Gpx), and superoxide dismutase (SOD) levels were reversed following treatment with HSP70. Additionally, MMP levels were reduced by 29.7, 46.4, 79.5, and 125.2 relative units following treatment with 5-20 mg/L of HSP70, respectively. HSP70 treatment also decreased levels of fragmented mitochondria and apoptosis, and mRNA and protein expressions of NF-κB and STAT3 were reduced by >25%. SIGNIFICANCE: Taken together, these findings indicate that supplementation with HSP70s recovered cell viability and MMP and reduced levels of ROS, apoptosis, and mitochondrial fragmentation. Additionally, supplementation with HSP70 significantly reduced the expressions of STAT3 and NF-κB.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/farmacologia , Inflamação/tratamento farmacológico , NF-kappa B/genética , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/tratamento farmacológico , Fator de Transcrição STAT3/genética , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Inflamação/genética , Doença de Parkinson Secundária/genética , RNA Mensageiro/genética , Rotenona
5.
Phytochemistry ; 165: 112055, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31261031

RESUMO

Twenty-one known Amaryllidaceae alkaloids of various structural types and one undescribed alkaloid, named narcimatuline, have been isolated from fresh bulbs of Narcissus pseudonarcissus L. cv. Dutch Master. The chemical structures were elucidated by combination of MS, HRMS, 1D and 2D NMR spectroscopic techniques, and by comparison with literature data. Narcimatuline amalgamates two basic scaffolds of Amaryllidaceae alkaloids in its core, namely galanthamine and galanthindole. All isolated compounds were evaluated for their in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), prolyl oligopeptidase (POP), and glycogen synthase kinase-3ß (GSK-3ß) inhibitory activities. The most interesting biological profile was demonstrated by newly isolated alkaloid narcimatuline.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Alcaloides de Amaryllidaceae/farmacologia , Inibidores da Colinesterase/farmacologia , Narcissus/química , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Relação Dose-Resposta a Droga , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Serina Endopeptidases/metabolismo , Relação Estrutura-Atividade
6.
Chem Biol Interact ; 310: 108738, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283913

RESUMO

Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. H2S is a gas neuromodulator which also possesses anti-oxidant and anti-inflammatory properties, and is found to play neuroprotective effect in neurodegenerative diseases. This study investigated the effect of endogenous and exogenous H2S in a mouse model of ischemic stroke. 129P2-Cbstm1Unc/J mice with heterozygous mutants in H2S generating enzyme cystathionine ß-synthase were used to study the effect of endogenous H2S. H2S donor NaHS was used as exogenous H2S. Animals were pretreated with H2S and then subjected to middle cerebral artery occlusion surgery. Behavioral outcome was evaluated by novel object recognition test. Inflammatory cytokines were measured using ELISA. Western blot was used to detect the activation of NF-κB. Aged 129P2-Cbstm1Unc/J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous H2S treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of H2S was mediated by inhibiting NF-κB. Our findings suggest that both endogenous and exogenous H2S are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury.


Assuntos
Sulfeto de Hidrogênio/uso terapêutico , Precondicionamento Isquêmico/métodos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Citocinas/metabolismo , Sulfeto de Hidrogênio/farmacologia , Infarto da Artéria Cerebral Média/complicações , Inflamação/tratamento farmacológico , Camundongos , NF-kappa B/metabolismo , Traumatismo por Reperfusão/prevenção & controle
7.
J Agric Food Chem ; 67(29): 8227-8234, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31299148

RESUMO

The mechanisms underlying neurodegenerative diseases are not fully understood yet. However, an increasing amount of evidence has suggested that these disorders are related to oxidative stress. We reported herein that lipoamide (LM), a neutral amide derivative of lipoic acid (LA), could resist oxidative stress-mediated neuronal cell damage. LM is more potent than LA in alleviating hydrogen peroxide- or 6-hydroxydopamine-induced PC12 cell injury. Our results reveal that LM promotes the nuclear accumulation of NFE2-related factor 2 (Nrf2), following with the activation of expression of Nrf2-governed antioxidant and detoxifying enzymes. Notably, silencing Nrf2 gene annuls the protection of LM, which demonstrates that Nrf2 is engaged in this cytoprotection. Our findings suggest that LM might be used as a potential therapeutic candidate for oxidative stress-related neurological disorders.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ácido Tióctico/análogos & derivados , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Ratos , Transdução de Sinais/efeitos dos fármacos , Ácido Tióctico/farmacologia
8.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2353-2358, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359663

RESUMO

In this paper, Xixian Tongshuan Preparation was used as the research object, and all the chemical components of the 13 traditional Chinese medicines were collected. The target finding technique was used to obtain the key targets of the neuroprotective effect of Xixian Tongshuan Preparation, including 5 glutamate receptors, TGFR-1 and VEGFR-2. Molecular docking technology was used to screen out the potential active components of the above targets and to analyze their mechanism of action. It was found that single component, such as neo-complanatoside and neo-carthamin, in Xixian Tongshuan Preparation could simultaneously act on different targets. The chemical constituents in Ligusticum chuanxiong, Angelica sinensis, Carthamus tinctorius, and Panax pseudo-ginseng could simultaneously act on different neuroprotective-related targets, which reflected the application of multi-components to multi-targets. Point and multiple sites played a key role in protecting neurons against cerebral ischemic injury. This study explains the multi-target mechanism of anti-cerebral ischemic injury in neuroprotection at the molecular level, and provides a certain direction for the clinical application and experimental research of Xixian Tongshuan Preparation.


Assuntos
Isquemia Encefálica , Infarto Cerebral , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Compostos Fitoquímicos/farmacologia , Humanos , Simulação de Acoplamento Molecular
9.
Life Sci ; 233: 116686, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31348946

RESUMO

Epilepsy is a neurological disorder characterized by an enduring predisposition to generate and aggravate epileptic seizures affecting around 1% of global population making it a serious health concern. Despite the recent advances in epilepsy research, no disease-modifying treatment able to terminate epileptogenesis have been reported yet reflecting the complexity in understanding the disease pathogenesis. To overcome the current treatment gap against epilepsy, one effective approach is to explore anti-epileptic effects from a drug that are approved to treat non-epileptic diseases. In this regard, Metformin emerged as an ideal candidate which is a first line treatment option for type 2 diabetes mellitus (T2DM), has conferred neuroprotection in several in vivo neurological disorders such as Alzheimer's diseases (AD), Parkinson's disease (PD), Stroke, Huntington's diseases (HD) including epilepsy. In addition, Metformin has ameliorated cognitive alteration, learning and memory induced by epilepsy as well as in animal model of AD. Herein, we review the promising findings demonstrated upon Metformin treatment against animal model of epilepsy however, the precise underlying mechanism of anti-epileptic potential of Metformin is not well understood. However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of α-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level. These reflects that Metformin being non-anti-epileptic drug (AED) has a potential to ameliorate the cellular pathways that were impaired in epilepsy reflecting its therapeutical potential against epileptic seizure that might plausibly overcome the limitations of today epilepsy treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Diabetes Mellitus Tipo 2/complicações , Epilepsia/etiologia
10.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2588-2593, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359728

RESUMO

The PK-PD correlation models by using pharmacodynamics and pharmacokinetics were applied to study the material basis of Naomaitong,a clinical empirical prescription for the treatment of cerebral apoplexy,in inhibiting the death of PC12 nerve cells induced by Na_2S_2O_4 and Glu. In this experiment,PC12 cell death models induced by Na_2S_2O_4 and Glu were established respectively.With LDH lateral leakage and NO content as pharmacodynamic indexes,PK-PD model was established by SVM algorithm to evaluate the effective components of Naomaitong in inhibiting neural cell death. The results showed that the positive correlation of emodin methyl ether-8-O-ß-D-glucopyranoside,aloe emodin,chrysophanol,rhein,emodin,ginsenoside Rg1,ginsenoside Rc,3'-methoxypuerarin and ligustilide was significant,obviously improving the LDH release and NO content. The results indicated that the contribution of Radix Puerariae Lobatae Radix and Rhei Radix et Rhizoma in Naomaitong could protect the nerve cell death induced by Na_2S_2O_4 and Glu respectively. PK-PD model was used to screen the neuroprotective components in Naomaitong,revealing the possible pharmacodynamic material basis of Naomaitong in the treatment of cerebral ischemia injury.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Animais , Células PC12 , Ratos
11.
Life Sci ; 232: 116618, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265854

RESUMO

AIMS: Mitochondrial dysfunction has been regarded as one of the hallmarks of cerebral ischemia-reperfusion injury. In previous studies, we have provided evidence that the extracellular signaling pathway (ERK) 1/2 inhibitor PD98059 improved the neurological deficits by modulating antioxidant and anti-apoptotic activities in rats subjected to cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Since oxidative stress can activate mitochondria-dependent apoptosis and autophagy, we further explored the effects of PD98059 on mitochondria involved with apoptosis and autophagy in rat CA model. MATERIALS AND METHODS: We disposed PD98059 in CA/CPR rats, tested the mitochondrial-mediated apoptosis pathway in brain tissues at 24 h post-resuscitation by mitochondrial permeability transition pores (MPTP), cytochrome c (CytC), BCL-2, BAX, caspase-3, as well as autophagy by LC3, Beclin-1, and p62. Furthermore, we explored the relationship of dynamin-related protein 1 (Drp1) with apoptosis and autophagy. KEY FINDINGS: Our study showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. SIGNIFICANCE: PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy at 24 h post-resuscitation in rats subjected to CA/CPR, which is linked with the downregulation of Drp1 expression.


Assuntos
Flavonoides/farmacologia , Parada Cardíaca/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Reanimação Cardiopulmonar , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Flavonoides/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
12.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2686-2690, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359678

RESUMO

To investigate the inhibitory effects and mechanism of Cistanche tubulosa ethanol extract( CTEE) against oxygen-glucose deprivation/reperfusion( OGD/R)-induced PC12 cells neuronal injury. In this study,OGD/R-induced PC12 cells were used to explore the neuroprotective effects of CTEE( 12. 5,25,50 mg·L-1) by detecting cell viability with MTT assay,apoptosis with AO/EB and Hoechst 33258,mitochondrial membrane potential changes with JC-1 staining,mitochondrial oxidative stress with MitoSOX staining,as well as the apoptosis-related protein expression( PARP,cleaved PARP,caspase-3,cleaved caspase-3,Bax,Bcl-2) with Western blot. RESULTS:: showed that CTEE effectively protected OGD/R-induced neuronal injury and increased the survival rate of PC12 cells.AO/EB and Hoechst 33258 staining showed that CTEE could effectively inhibit apoptosis. Moreover,JC-1 and MitoSOX staining results showed that CTEE decreased mitochondrial stress and mitochondrial membrane potential imbalance in PC12 cells in a concentration-dependent manner. Meanwhile,CTEE could obviously suppress the activation of key proteins in mitochondrial apoptosis pathway such as caspase-3 and PARP,and significantly inhibit the rise of Bax and down-regulation of Bcl-2. In conclusion,CTEE has obvious protective effects on OGD/R-induced PC12 cells neuronal injury,potentially via inhibiting mitochondrial oxidative stress and apoptosis-related signaling pathway.


Assuntos
Apoptose , Cistanche/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Animais , Caspase 3/metabolismo , Etanol , Glucose , Estresse Oxidativo , Oxigênio , Células PC12 , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Proteína X Associada a bcl-2/metabolismo
13.
Life Sci ; 232: 116647, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301416

RESUMO

AIM: Brain injury after sepsis leads to high mortality and long-term brain dysfunction in patients. Previous studies revealed that borneol has a protective effect on the brain, but its function on sepsis associated encephalopathy (SAE) remains unknown. Herein, we investigated the protective effect of borneol against sepsis-related brain injury. MAIN METHODS: Lipopolysaccharide (LPS)-induced sepsis mice and cells were treated with borneol at the dose of 100 mg/kg by gavage or 10 µg/ml in culture, respectively. The protective effect of borneol on neurons and the microglia were assessed in vivo and in vitro. KEY FINDINGS: We observed that borneol attenuated brain neuronal and microglial inflammation in LPS-induced sepsis mice with a suppression of p-p65 and p38 signaling that were initially activated by LPS in the brain. In vitro examination confirmed that the protective effect of borneol on both neurons and microglia, and its suppressive effect on p-p65 and p38 pathways were, at least in part, direct. SIGNIFICANCE: An early protection of neurons and microglia from bacterial endotoxin during sepsis is beneficial, and borneol has the potential to protect these cells.


Assuntos
Bornanos/uso terapêutico , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Endotoxinas/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Sepse/complicações , Animais , Bornanos/administração & dosagem , Bornanos/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia
14.
Khirurgiia (Mosk) ; (5): 57-63, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31169820

RESUMO

AIM: To study the effectiveness of intraoperative administration of Cytoflavine for the prevention of ischemic brain injury during cerebral aneurysm (CA) clipping with temporary occlusion of the leading artery under general anesthesia. MATERIAL AND METHODS: The prospective cohort single-center study included 40 patients with CA ( the main group - 27 patients with intraoperative administration of cytoflavine; the comparison group -13 patients without use of cytoflavine), who underwent aneurism clipping with temporary occlusion of the afferent artery. We assesed the intraoperative state of the brain, the time of awakening and extubation of patients after surgery, neurological deficit and local ischemic changes in the area of surgery according to the CT of the brain in the early postoperative period, resuscitation bed-day and the relationship of these indicators with the duration of temporary occlusion of the afferent artery in the selected groups of patients. RESULTS: In intergroup comparison, patients of the main group treated with intraoperative cytoflavin showed a reduction in the time of awakening (p=0.013) and the time of extubation (p=0.01) both with temporary occlusion of the afferent artery and in patients without temporary occlusion (p<0.05). The duration of resuscitation bed-day decreased in the main group of patients receiving intraoperatively cytoflavine (p=0.01), as well as in patients in the comparison group without temporary occlusion (p<0.05). CONCLUSION: Temporary occlusion of the afferent artery with short intervals of vessel occlusion in combination with intraoperative intravenous administration of cytoflavine expands the tolerability to artery occlusion in patients operated in the 'cold' period, reduces the possibility of neurological deficit, reduces the recovery period and resuscitation bed-day after surgical clipping CA.


Assuntos
Lesões Encefálicas/prevenção & controle , Isquemia Encefálica/fisiopatologia , Encéfalo/irrigação sanguínea , Mononucleotídeo de Flavina/administração & dosagem , Inosina Difosfato/administração & dosagem , Aneurisma Intracraniano/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Procedimentos Neurocirúrgicos/efeitos adversos , Niacinamida/administração & dosagem , Succinatos/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Lesões Encefálicas/etiologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/cirurgia , Isquemia Encefálica/etiologia , Isquemia Encefálica/cirurgia , Combinação de Medicamentos , Mononucleotídeo de Flavina/farmacologia , Humanos , Inosina Difosfato/farmacologia , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/cirurgia , Cuidados Intraoperatórios , Fármacos Neuroprotetores/farmacologia , Procedimentos Neurocirúrgicos/métodos , Niacinamida/farmacologia , Estudos Prospectivos , Succinatos/farmacologia , Técnicas de Sutura
15.
Cell Physiol Biochem ; 53(1): 76-86, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192545

RESUMO

BACKGROUND/AIMS: Diabetes causes damage to the enteric nervous system. The enteric nervous system consists of neurons and enteric glial cells (EGCs). The present study evaluated the effects of an ethyl-acetate fraction (EAF) from Trichilia catigua (T. catigua; 200 mg/kg) on the total population of enteric neurons (HuC/D-immunoreactive [IR]) and EGCs (S100-IR and glial fibrillary acidic protein [GFAP]-IR) in the total preparation and jejunal mucosa in diabetic rats. METHODS: The animals were distributed into four groups: normoglycemic rats (N), diabetic rats (D), normoglycemic rats that received the EAF (NC), and diabetic rats that received the EAF (DC). The jejunum was processed for immunohistochemistry to evaluate HuC/D, S100, and GFAP immunoreactivity. The expression of S100 and GFAP proteins was also quantified by Western blot. RESULTS: The D group exhibited a decrease in the number of neurons and EGCs, an increase in the area of cell bodies, an increase in S100 protein expression, a decrease in GFAP protein expression, and a decrease in S100-IR and GFAP-IR EGCs in the jejunal mucosa. The DC group exhibited a decrease in the number of neurons and EGCs, a decrease in the area of cell bodies, a decrease in S100 and GFAP protein expression, and a decrease in S100-IR and GFAP-IR EGCs in the jejunal mucosa. The NC group exhibited maintenance of the number of neurons and EGCs, an increase in the area of cell bodies, and a decrease in S100 and GFAP protein expression. CONCLUSION: The EAF from T. catigua partially conferred protection against diabetic neuropathy in the enteric nervous system.


Assuntos
Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/prevenção & controle , Jejuno/inervação , Meliaceae/química , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Acetatos/química , Animais , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/patologia , Sistema Nervoso Entérico/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/análise , Jejuno/efeitos dos fármacos , Jejuno/patologia , Masculino , Neuroglia/patologia , Neurônios/patologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Proteínas S100/análise
16.
Paediatr Drugs ; 21(3): 137-152, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31155694

RESUMO

Pediatric-onset multiple sclerosis (MS) comprises 2-5% of MS cases, and is known to be associated with high disease activity and the accumulation of disability at an earlier age than their adult-onset counterparts. Appropriate therapy leading to disease control has the potential to alter the known trajectory of adverse long-term physical, cognitive, and psychosocial outcomes in this population. Thus, optimizing treatment for children and adolescents with MS is of paramount importance. The last decade has seen a growing number of disease-modifying therapies approved for relapsing MS in adults, and available agents now include oral, injectable, and infusion therapies. Recently, the development of randomized controlled MS trials in youth has led to the first agent approved by the US FDA for the treatment of pediatric MS-fingolimod. With this, we have entered a new era of knowledge and treatment in this population and ongoing pediatric trials are expected to further inform clinical management. With the emergence of highly effective therapies targeting the inflammatory component of the disease, there has been increased interest in identifying treatment strategies that instead target mechanisms such as remyelination/repair, neuroprotection, or rehabilitation. The potential role for such emerging therapies in the treatment of pediatric MS remains an important area of study. In this review, we discuss current evidence for MS therapies in children including the treatment of acute relapses, disease-modifying therapies, and symptomatic management. We will also discuss evidence for emerging therapies, including remyelinating and neuroprotective agents.


Assuntos
Esclerose Múltipla/terapia , Fármacos Neuroprotetores/uso terapêutico , Adolescente , Feminino , Humanos , Masculino , Esclerose Múltipla/patologia , Fármacos Neuroprotetores/farmacologia , Resultado do Tratamento
17.
Chem Biol Interact ; 308: 332-338, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170386

RESUMO

BACKGROUND: Sevoflurane (sevo) has been reported to be an effective neuroprotective agent in cerebral ischemia/reperfusion injury (CIRI). However, the precise molecular mechanism underlying sevo preconditioning in CIRI remains largely unknown. METHODS: A middle cerebral artery occlusion (MCAO) rat model and primary cortical neurons after oxygen-glucose deprivation and reoxygenation (OGDR) were used as the in vivo and in vitro models of CIRI. The expression profiles of miR-181a and X chromosome-linked inhibitor-of-apoptosis protein (XIAP) in the cerebral cortex of rats and in cortical neurons were examined by qRT-PCR and Western blot, respectively. The infarct volumes were measured by TTC staining and neurological deficits in rats was determined by Zea-Longa scoring criteria. The cell viability, lactate dehydrogenase (LDH) release and apoptotic rate were detected in cortical neurons by MTT assay, LDH analysis and flow cytometry. Western blot analysis was performed to assess the expression of apoptosis-related protein. Luciferase reporter assay was used to confirm the interaction between miR-181a and XIAP. RESULTS: miR-181a was upregulated and XIAP was downregulated in rats after MCAO. Sevo preconditioning attenuated miR-181a expression and promoted XIAP level in a rat model of CIRI. Sevo preconditioning ameliorated anti-miR-181a-mediated protective effects on cerebral ischemia in rat model of CIRI, presented as the decrease of infarct volume, neurological deficit and apoptosis. Moreover, sevo pretreatment abated miR-181a-induced cellular injury in primary cortical neurons after OGD, embodied by the increase of cell viability, the reduction of LDH release and the decline of apoptosis. Furthermore, miR-181a suppressed XIAP expression by binding to its 3'UTR in cortical neurons, and sevo-mediated increase on XIAP expression was counteracted by miR-181 overexpression in OGDR-treated neurons. CONCLUSION: Sevo preconditioning protected against CIRI in vitro and in vivo possibly by inhibiting miR-181a and facilitating XIAP.


Assuntos
MicroRNAs/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Sequência de Bases , Regulação para Baixo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Proteínas Inibidoras de Apoptose/química , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Alinhamento de Sequência , Sevoflurano/farmacologia
18.
Phytochemistry ; 165: 112049, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31229788

RESUMO

Five undescribed phenolic compounds, inclusing a depsidone derivative, hyperwightin A, a flavone derivative, hyperwightin B, and three benzophenone glycosides, hyperwightins C-E, along with four known ones were isolated from the 95% EtOH extract of the whole plants of Hypericum wightianum. Structures of the obtained compounds were elucidated by spectroscopic analyses. The protective effects of the isolates against corticosterone-induced PC12 cell injury were assessed. Hyperwightin E, petiolin G and hyperxanthone exhibited noticeable neuroprotection at 10 µM.


Assuntos
Hypericum/química , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Corticosterona/antagonistas & inibidores , Corticosterona/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Fenóis/química , Fenóis/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Ratos
19.
Dokl Biochem Biophys ; 485(1): 141-144, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31201636

RESUMO

It was established that in neurodegeneration models in the human neuron-like cell line SH-SY5Y, amide derivatives of arachidonic and docosahexaenoic acids were inactive in experiments with MPP+ and CoCl2 but protected from H2O2. The protective activity of neurolipins decreased in the series DHA-DA > AA-SER ≥ AA-GLY > AA-GABA ≥ AA-EA and was manifested starting from a concentration of 0.5 nM.


Assuntos
Amidas , Ácidos Graxos , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores , Transdução de Sinais/efeitos dos fármacos , Amidas/química , Amidas/farmacologia , Linhagem Celular , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Humanos , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia
20.
DNA Cell Biol ; 38(8): 874-879, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215797

RESUMO

Microglia-mediated neuroinflammation plays an important role in Alzheimer's disease development. Resveratrol, a natural polyphenol from the Japanese knotweed (Polygonum cuspidatumand), is known to protect against neuroinflammation, but the mechanism remains unclear. To begin to explore potential mechanisms, we created a model of inflammatory injury in BV-2 murine microglial cells based on the induction of amyloid-ß. We found that resveratrol (10 and 50 nM) significantly inhibited Aß-induced proliferation and activation of BV-2 cells, as well as their release of the proinflammatory cytokines, IL-6 and TNF-α. Resveratrol also suppressed the overexpression of cleaved caspase-1 and IL-1ß, and decreased Aß-stimulated degradation of IkBα and phosphorylation of NF-κB phosphorylation. Western blot analysis showed that Aß upregulated the TXNIP/TRX/NLRP3 pathway, while resveratrol treatment inhibited it. We conclude that resveratrol protects microglia from Aß-stimulated inflammation by suppressing the inflammatory response, at least in part by inhibiting the TXNIP/TRX/NLRP3 signaling pathway.


Assuntos
Proteínas de Transporte/metabolismo , Microglia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Resveratrol/farmacologia , Tiorredoxinas/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Caspase 1/metabolismo , Linhagem Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Microglia/fisiologia , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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