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1.
Cochrane Database Syst Rev ; 2: CD013306, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33704781

RESUMO

BACKGROUND: Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events. OBJECTIVES: (1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020. SELECTION CRITERIA: We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods. MAIN RESULTS: We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) -0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95% confidence interval (CI) -1.44 to -0.40; high-certainty evidence). Donepezil 10 mg (MD -2.21 ADAS-Cog points, 95% CI -3.07 to -1.35; moderate-certainty evidence) and galantamine 16 to 24 mg (MD -2.01 ADAS-Cog point, 95%CI -3.18 to -0.85; moderate-certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI -3.04 to 3.10; low-certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence). In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes. AUTHORS' CONCLUSIONS: We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches.


Assuntos
Inibidores da Colinesterase/administração & dosagem , Demência Vascular/tratamento farmacológico , Donepezila/administração & dosagem , Galantamina/administração & dosagem , Metanálise em Rede , Rivastigmina/administração & dosagem , Atividades Cotidianas , Viés , Inibidores da Colinesterase/efeitos adversos , Cognição/efeitos dos fármacos , Donepezila/efeitos adversos , Galantamina/efeitos adversos , Humanos , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos , Desempenho Físico Funcional , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivastigmina/efeitos adversos
2.
Zhongguo Zhong Yao Za Zhi ; 46(1): 247-252, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645076

RESUMO

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.


Assuntos
Demência Vascular , Medicamentos de Ervas Chinesas , Medicina , Salvia miltiorrhiza , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Injeções
3.
Medicine (Baltimore) ; 99(46): e23236, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181711

RESUMO

BACKGROUND: Butylphthalide is widely used for the adjunctive treatment of vascular dementia; however, the clinical evidences are not well synthesized yet. METHODS: We proposed a systematic review and meta-analysis to evaluate the efficacy and safety of butylphthalide as adjunctive therapy for vascular dementia. Seven electronic databases (China National Knowledge Infrastructure, Wanfang database, Chongqing VIP database, China Biomedical Literature Database, Pubmed, EMBASE and Cochrane library) will be searched for eligible randomized controlled trials (RCTs). Required data of included studies will be collected. Quality of studies will be evaluated using Cochrane risk of bias assessment tool. Data synthesis will be performed using Review Manager software. Subgroup analysis and sensitivity analysis will also be carried. RESULTS: Synthesis results of current available RCTs regarding the efficacy and safety of butylphthalide for the treatment vascular dementia will be provided by this systematic review and meta-analysis. CONCLUSION: This systematic review and meta-analysis will provide high level evidence of butylphthalide clinical application. REGISTRATION: PROSPERO CRD42020168947.


Assuntos
Benzofuranos/uso terapêutico , Protocolos Clínicos , Demência Vascular/tratamento farmacológico , Benzofuranos/farmacologia , Benzofuranos/normas , Demência Vascular/fisiopatologia , Humanos , Metanálise como Assunto , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/normas , Inibidores da Agregação de Plaquetas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(40): e22455, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019432

RESUMO

BACKGROUND: Cerebral small vessel disease (CSVD) is the most common etiology of vascular cognitive impairment (VCI). VCI in CSVD (CSVD-VCI) shows a progressive course with multiple stages and is also associated with dysfunctions such as gait, emotional and behavioral, and urinary disturbances, which seriously affect the life quality of elderly people. In mainland China, Chinese herbal medicine (CHM) is clinically used for CSVD-VCI and presenting positive efficacy, but the evidence revealed in relevant clinical trials has not been systematically evaluated. The purpose of this study is to assess the current evidence available for the clinical efficacy and safety of CHM for CSVD-VCI. METHODS: A literature search of published RCTs up to April 30, 2020, has been conducted in the following 7 electronic databases: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science and Technology Journals Database (VIP), Wanfang Database, and Chinese Biomedical Literature Service System (SinoMed). For unpublished studies, 2 clinical trial online registration websites will be searched: ClinicalTrials.gov and Chinese Clinical Trial Registry (ChiCTR). Only randomized controlled trials (RCTs) using CHM in the treatment of patients with CSVD-VCI, which compares CHM with no treatment, placebo, or other conventional treatments, will be included in this systematic review. Primary outcomes will be set as acknowledged scales measuring cognitive function. Secondary outcomes will involve activities of daily living, behavioral, and psychological symptoms, global performance of dementia, neurological function, biological markers of endothelial dysfunction, the clinical effective rate, and adverse events. After screening studies and extracting data, the Cochrane Collaborations tool for assessing risk of bias will be applied to assess the methodological quality of included RCTs. Review Manager Version 5.3 software will be used for data synthesis and statistical analysis. Subgroup analyses, sensitivity analyses, and meta-regression will be conducted to detect potential sources of heterogeneity. The funnel plot and Eggers test will be developed to evaluate publication bias, if available. We will perform the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to appraise the quality of evidence. RESULTS: Evidence exhibited in this systematic review will provide practical references in the field of CHM treating CSVD-VCI. Moreover, our detailed appraisals of methodological deficiencies of relevant RCTs will offer helpful advice for researchers who are designing trials of CHMs in the treatment of CSVD-VCI. CONCLUSION: The conclusion about the clinical efficacy and safety of CHM for CSVD-VCI will be provided for clinical plans, decisions, and policy developments in the full version of this systematic review. SYSTEMATIC REVIEW REGISTRATION: INPLASY202080120.


Assuntos
Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Doenças de Pequenos Vasos Cerebrais/complicações , Demência Vascular/etiologia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
5.
Medicine (Baltimore) ; 99(37): e22209, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925798

RESUMO

BACKGROUND: Vascular dementia has become the second most common type of dementia after Alzheimer disease. At present, there is no uniform standard for VaD treatment guidelines among countries. The efficacy of ginkgo biloba in the treatment of vascular dementia is still controversial. The purpose of this study is to evaluate the effectiveness and safety of ginkgo biloba in the treatment of vascular dementia through meta-analysis. METHODS: Six English databases (PubMed, Web of science, Medline, EBASE, Springer Cochrane Library, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wan fang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database(CNKI) and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to August 1, 2020. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Any disagreement will be resolved by discussion with the third reviewer. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. The change in the scores on mini-mental state examination, activity of daily living scale and Montreal cognitive assement will be used as the main outcome measure, Hamilton depression scale, Hastgawa dementia scale, blessed dementia scale, clinical dmentia rating scale as the secondary outcome. Treatment emergent symptom scale, general physical examination (temperature, pulse, respiration, blood pressure), Routine examination of blood, urine and stool, electrocardiogram, liver and kidney function examination as the security indexs. RevMan5.3.5 will be used for meta-analysis. RESULTS: This study will provide high-quality evidence to assess the effectiveness and safety of ginkgo preparation for vascular dementia. CONCLUSION: This systematic review will explore whether ginkgo preparation is an effective and safe intervention for vascular dementia. ETHICS AND DISSEMINATION: Ethical approval are not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and will be shared on social media platforms. This review will be disseminated in a peer-reviewed journal or conference presentation. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020167851.


Assuntos
Demência Vascular/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Atividades Cotidianas , Demência Vascular/epidemiologia , Depressão/epidemiologia , Nível de Saúde , Humanos , Testes de Estado Mental e Demência , Extratos Vegetais/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
6.
Adv Exp Med Biol ; 1195: 213-225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468480

RESUMO

Vascular dementia (VaD) is well recognized as the second most familiar form of dementia in the aged population. The present study is aimed to investigate the neuroprotective effects of ethanolic extract of leaves of Ocimum sanctum (EEOS) against hyperhomocysteinemia (HHcy)-induced vascular dementia (VaD) in Wistar rats. HHcy was induced by administering L-methionine (1.7 g/kg, p.o) for 4 weeks. Donepezil (0.1 mg/kg, p.o.) and EEOS (100 mg/kg, 200 mg/kg, 400 mg/kg, p.o.) were administered from the 14th day of L-methionine treatment. The behavioral impairment caused due to HHcy in rats was assessed by the Morris water maze (MWM) and Y-maze tests using a video tracking system. Biochemical estimations and aortic ring assay were also performed followed by a molecular docking analysis of active chemical constituents present in the leaves of Ocimum sanctum Linn. In this study, the EEOS treatment in hyperhomocysteinemic rats has showed significant improvement in spatial learning and working memory performance. The EEOS treatment further increased nitric oxide bioavailability and significantly altered all serum and brain biochemical parameters in a dose-dependent manner. The docking analysis revealed that among all the phytoconstituents of Ocimum sanctum compound (IX), molludistin has showed good inhibitory activity against S-adenosyl homocysteine, thus preventing homocysteine formation and may be responsible for potential effects of EEOS against HHcy-induced VaD. From our results, we conclude that EEOS can be used as a promising adjunct therapy for treatment of HHcy-induced VaD and oxidative stress.


Assuntos
Demência Vascular/tratamento farmacológico , Demência Vascular/etiologia , Hiper-Homocisteinemia/complicações , Ocimum sanctum/química , Extratos Vegetais/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Demência Vascular/sangue , Demência Vascular/metabolismo , Homocisteína/sangue , Homocisteína/metabolismo , Hiper-Homocisteinemia/sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
7.
J Med Chem ; 63(6): 3370-3380, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32115956

RESUMO

To validate PDE4 inhibitors as novel therapeutic agents against vascular dementia (VaD), 25 derivatives were discovered from the natural inhibitor α-mangostin (IC50 = 1.31 µM). Hit-to-lead optimization identified a novel and selective PDE4 inhibitor 4e (IC50 = 17 nM), which adopted a different binding pattern from PDE4 inhibitors roflumilast and rolipram. Oral administration of 4e at a dose of 10 mg/kg exhibited remarkable therapeutic effects in a VaD model and did not cause emesis to beagle dogs, indicating its potential as a novel anti-VaD agent.


Assuntos
Demência Vascular/tratamento farmacológico , Inibidores da Fosfodiesterase 4/uso terapêutico , Xantonas/uso terapêutico , Aminopiridinas/metabolismo , Animais , Benzamidas/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Ciclopropanos/metabolismo , Cães , Desenho de Fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Inibidores da Fosfodiesterase 4/síntese química , Inibidores da Fosfodiesterase 4/metabolismo , Inibidores da Fosfodiesterase 4/farmacocinética , Ligação Proteica , Rolipram/metabolismo , Rolipram/uso terapêutico , Relação Estrutura-Atividade , Vômito/prevenção & controle , Xantonas/síntese química , Xantonas/metabolismo , Xantonas/farmacocinética
8.
PLoS One ; 15(2): e0227820, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32032361

RESUMO

Cognitive impairment is a common complication observed after a stroke. Currently there are no definitively proven pharmacologic therapies for recovery from post-stroke cognitive impairment and vascular dementia. In this meta-analysis, we evaluated the efficacy and safety of cholinesterase inhibitors in their improvement of cognition in patients with post-stroke cognitive impairment and vascular dementia. We conducted a meta-analysis using seven eligible studies from 305 published articles. We investigated the differences in Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, before and after cholinergic augmentation in patients with post-stroke cognitive impairment and vascular dementia. MMSE and ADAS-cog scores were also compared during the subsequent follow-up periods. MMSE score of patients with post-stroke cognitive impairment was increased after cholinergic augmentation throughout the 24 weeks with mean differences [MD] of 3.000, 1.732, 1.578 1.516, and 1.222, at 4, 4-8, 8-12, 12-18, and 18-24 weeks, respectively. In addition, ADAS-cog scores decreased at 6, 12, 18, and 24 weeks by pharmaceutical augmentation, but not with placebo with mean differences [MD] of -2.333, -2.913, -2.767, -2.416, and -1.859, respectively. This meta-analysis shows that acetylcholinesterase inhibitors maintain a stable pattern of improved cognitive function in patients with post stroke cognitive impairment and vascular dementia without the increased risk of side effects.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Demência Vascular/tratamento farmacológico , Demência Vascular/etiologia , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Inibidores da Colinesterase/efeitos adversos , Inibidores da Colinesterase/farmacologia , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade
9.
Medicine (Baltimore) ; 99(4): e18507, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977846

RESUMO

BACKGROUND: Although memory loss and other symptoms of dementia pose tremendous burdens on patients and societies, there is currently no cure for dementia. METHODS: We conducted a systematic review and meta-analysis of the anti-dementia effects of Danggui-Shaoyao-San (DSS), which is derived from natural resources. We searched for randomized controlled trials (RCTs) from inception to June 2019. We searched PubMed, Embase, Korean databases (Research Information Service System and Oriental Medicine Advanced Searching Integrated System), Chinese databases (China Knowledge Resource Integrated Database and Wanfang Database), and Japanese databases (CiNii and J-STAGE). Studies were included if they were a RCT, investigated the efficacy of DSS or its modified form, and included participants with dementia. Use of DSS with other treatment (eg, acupuncture, anti-dementia drugs, etc) was included. Items of each trial were evaluated by 2 independent reviewers. Data were pooled by using random-effect models. RESULTS: A total of 482 studies were identified, and 5 eligible studies for Alzheimer disease (AD) and 4 studies for vascular dementia (VD) were included in the final analysis, representing a total of 567 participants. As for AD, pooled results of the Mini-Mental State Examination (MMSE) (mean differences [MD] 4.60; 95% confidence interval [CI] 4.29, 4.91) and activities of daily living (MD 11.40; 95% CI 10.94, 11.86) favored DSS. DSS had synergistic effect with acupuncture over acupuncture alone in MMSE (MD 1.69; 95% CI 1.05, 2.34), Hasegawa Dementia Scale (MD.62; 95% CI -0.20, 1.44), and activities of daily living (MD 2.38; 95% CI 1.92, 2.85). In VD, pooled results showed a significant difference in the score of dementia scales such as MMSE and Hasegawa Dementia Scale compared with nootropic drugs. DSS significantly reduced symptoms (odds ratio 5.02, 95%, CI 2.76-9.11) in patients with VD. The respective size of each RCTs was small and some included studies were of low quality due to their limited description on methodological issues. CONCLUSION: These estimates suggest that DSS provides clinically important reductions in symptoms of AD and VD and can be a promising anti-dementia drug candidate.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Atividades Cotidianas , Terapia por Acupuntura/métodos , China , Terapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Testes de Estado Mental e Demência , Nootrópicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Sci Rep ; 10(1): 257, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937840

RESUMO

Dementia is a major cause of disability and dependency among older people. If the lives of people with dementia are to be improved, research and its translation into druggable target are crucial. Ancient systems of healthcare (Ayurveda, Siddha, Unani and Sowa-Rigpa) have been used from centuries for the treatment vascular diseases and dementia. This traditional knowledge can be transformed into novel targets through robust interplay of network pharmacology (NetP) with reverse pharmacology (RevP), without ignoring cutting edge biomedical data. This work demonstrates interaction between recent and traditional data, and aimed at selection of most promising targets for guiding wet lab validations. PROTEOME, DisGeNE, DISEASES and DrugBank databases were used for selection of genes associated with pathogenesis and treatment of vascular dementia (VaD). The selection of new potential drug targets was made by methods of NetP (DIAMOnD algorithm, enrichment analysis of KEGG pathways and biological processes of Gene Ontology) and manual expert analysis. The structures of 1976 phytomolecules from the 573 Indian medicinal plants traditionally used for the treatment of dementia and vascular diseases were used for computational estimation of their interactions with new predicted VaD-related drug targets by RevP approach based on PASS (Prediction of Activity Spectra for Substances) software. We found 147 known genes associated with vascular dementia based on the analysis of the databases with gene-disease associations. Six hundred novel targets were selected by NetP methods based on 147 gene associations. The analysis of the predicted interactions between 1976 phytomolecules and 600 NetP predicted targets leaded to the selection of 10 potential drug targets for the treatment of VaD. The translational value of these targets is discussed herewith. Twenty four drugs interacting with 10 selected targets were identified from DrugBank. These drugs have not been yet studied for the treatment of VaD and may be investigated in this field for their repositioning. The relation between inhibition of two selected targets (GSK-3, PTP1B) and the treatment of VaD was confirmed by the experimental studies on animals and reported separately in our recent publications.


Assuntos
Demência Vascular/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos/métodos , Terapia de Alvo Molecular , Bases de Dados Factuais , Farmacologia , Interface Usuário-Computador
11.
Eur J Med Chem ; 187: 111915, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31838329

RESUMO

A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4-15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5H-dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment.


Assuntos
Azepinas/farmacologia , Clomipramina/análogos & derivados , Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Azepinas/química , Linhagem Celular Tumoral , Clomipramina/química , Clomipramina/farmacologia , Disfunção Cognitiva/metabolismo , Demência Vascular/metabolismo , Relação Dose-Resposta a Droga , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Substâncias Protetoras/síntese química , Substâncias Protetoras/química , Relação Estrutura-Atividade
12.
Medicine (Baltimore) ; 98(50): e18326, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852125

RESUMO

BACKGROUND: Vascular dementia (VaD) is the second most common cause of dementia. The treatment of VaD still remains a challenge so far. Traditional Chinese Herbal medicine is a promising therapy due to their multiple components and targets. Shenmayizhi decoction (SMYZD), a Chinese Herbal prescription, has been reported its effective in alleviating cognitive dysfunction in clinical practice. However, strong clinical research of SMYZD in the treatment of VaD was lack. Therefore, we design this study to evaluate the adjuvant role of SMYZD in the treatment of VaD. METHODS: This is a multicenter, randomized, blind, controlled trial. A total of 196 eligible patients will be assigned to receive Ginkgo biloba extracts (GBEs) plus SMYZD granule or GBEs plus SMYZD mimetic granule in a 1:1 ratio. The duration of the trial will be 12 weeks, and a follow-up will be performed at the 24th week. The primary outcomes are the National Institute of Health stroke scale (NIHSS) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcomes include the Mini-Mental State Examination (MMSE), the traditional Chinese Medicine (TCM) syndrome scale, Activities of Daily Living (ADL), concentrations of hypersensitive C-reactive protein (Hs-CRP), neuron-specific enolase (NSE) and homocysteine (HCY) in serum. Researchers will record any adverse events throughout the trial. DISCUSSION: This study will provide evidences to evaluate the efficacy and safety of SMYZD in combination with GBEs in treatment of VaD, as well as the adjuvant role of SMYZD in combination. TRIAL IS REGISTERED AT CHINESE CLINICAL TRIAL REGISTRY: ChiCTR1800017359.


Assuntos
Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Atividades Cotidianas , Idoso , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Extratos Vegetais/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Sci Rep ; 9(1): 18248, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796756

RESUMO

Vascular dementia (VaD) is a complex disorder caused by reduced blood flow in the brain. However, there is no effective pharmacological treatment option available until now. Here, we reported that low-dose levamlodipine besylate could reverse the cognitive impairment in VaD mice model of right unilateral common carotid arteries occlusion (rUCCAO). Oral administration of levamlodipine besylate (0.1 mg/kg) could reduce the latency to find the hidden platform in the MWM test as compared to the vehicle group. Furthermore, vehicle-treated mice revealed reduced phospho-CaMKII (Thr286) levels in the hippocampus, which can be partially restored by levamlodipine besylate (0.1 mg/kg and 0.5 mg/kg) treatment. No significant outcome on microglia and astrocytes were observed following levamlodipine besylate treatment. This data reveal novel findings of the therapeutic potential of low-dose levamlodipine besylate that could considerably enhance the cognitive function in VaD mice.


Assuntos
Demência Vascular/tratamento farmacológico , Niacina/análogos & derivados , Nootrópicos/uso terapêutico , Anlodipino , Animais , Astrócitos/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Microglia/efeitos dos fármacos , Niacina/administração & dosagem , Niacina/uso terapêutico , Nootrópicos/administração & dosagem
14.
Cochrane Database Syst Rev ; 2019(11)2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710397

RESUMO

BACKGROUND: Although vascular dementia is the second most common cause of dementia globally, evidence-based treatments are still lacking. Cerebrolysin is a porcine brain-derived preparation that is said to have neurotrophic and neuroprotective activity. In many parts of the world Cerebrolysin, given as a series of daily intravenous infusions, is used as a potential intervention for vascular dementia. A previous Cochrane Review on Cerebrolysin in vascular dementia yielded inconsistent results. We wished to update the review to add new studies from the international literature and employ contemporary methods for appraising the strength of the evidence. This is the first update of a review first published in 2013. OBJECTIVES: Primary: to assess the effect of Cerebrolysin on cognitive function, global function, and all-cause mortality in people living with vascular dementia. Secondary: to assess the adverse effects of Cerebrolysin and to assess the effect of Cerebrolysin on quality of life and caregiver burden. SEARCH METHODS: We searched ALOIS, MEDLINE, Embase, PsycINFO, CINAHL, ISI Web of Knowledge, LILACS, the Cochrane Library, ClinicalTrials.gov, and the WHO ICTRP on 16 June 2017, 9 May 2018, and 9 May 2019. We expanded the search by adding four Chinese databases, searched from 1 January 2012 to 19 May 2019. We checked bibliographies of relevant papers identified and contacted pharmaceutical companies, trial authors, and experts in the field to identify any additional published or unpublished data. SELECTION CRITERIA: We included all randomised controlled trials of Cerebrolysin used in people living with vascular dementia. We applied no language restriction. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and evaluated their methodological quality. Data were extracted and analysed using mean differences (MDs) or standardised mean differences (SMDs) with 95% confidence intervals (95% CI) for continuous outcomes. We reported dichotomous outcomes as risk ratio (RR) with 95% CI. We assessed the strength of the available evidence using the GRADE approach. MAIN RESULTS: We identified six randomised controlled trials with a total of 597 participants that were eligible for inclusion in the 2013 review. No new studies were eligible for inclusion in this update. Participants in the included studies, where dementia severity was reported, had mild to moderate severity of vascular dementia (four trials). The included studies tested varying doses and duration of Cerebrolysin treatment. Follow-up ranged from 15 days to three years. Five of included studies were conducted in China (three studies), Russia (one study), and Romania (one study), while relevant information of other study was unclear. Where details of funding were available, all studies were supported by the pharmaceutical industry (three studies). Cognitive function was measured using the Mini-Mental State Examination (MMSE) or Alzheimer's Disease Assessment Scale Cognitive Subpart, extended version (ADAS-cog+). Combining the MMSE and ADAS-cog+ data (three studies, 420 people), there was a beneficial effect of Cerebrolysin (SMD 0.36, 95% CI 0.13 to 0.58; very low-quality evidence). Global function was measured by Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC+) or Investigator's Clinical Global Impression (CGI). We assessed response rates on these measures (the proportion of participants with a CIBIC+ score of < 3; or at least moderate improvement of the CGI rating at the last visit). There was a beneficial effect of Cerebrolysin (two studies, 379 participants, RR 2.69, 95% CI 1.82 to 3.98; very low-quality evidence). Only one trial described mortality and reported no deaths. Four studies reported adverse events; data from two studies (379 people) were in a format that permitted meta-analysis, and there was no difference in rates of adverse effects (RR 0.91, 95% CI 0.29 to 2.85; very low-quality evidence). No studies reported on quality of life or caregiver burden. AUTHORS' CONCLUSIONS: Courses of intravenous Cerebrolysin improved cognition and general function in people living with vascular dementia, with no suggestion of adverse effects. However, these data are not definitive. Our analyses were limited by heterogeneity, and the included papers had high risk of bias. If there are benefits of Cerebrolysin, the effects may be too small to be clinically meaningful. There have been no new studies of Cerebrolysin in vascular dementia since the last Cochrane Review. Cerebrolysin continues to be used and promoted as a treatment for vascular dementia, but the supporting evidence base is weak. Adequately powered, methodologically robust trials are needed to properly assess the effects of Cerebrolysin in vascular dementia.


Assuntos
Aminoácidos/uso terapêutico , Demência Vascular/tratamento farmacológico , Nootrópicos/uso terapêutico , Aminoácidos/efeitos adversos , Cognição/efeitos dos fármacos , Efeitos Psicossociais da Doença , Demência Vascular/psicologia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Braz J Med Biol Res ; 52(11): e8371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721903

RESUMO

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirrolidinas/administração & dosagem , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Demência Vascular/metabolismo , Demência Vascular/fisiopatologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
16.
Mol Med Rep ; 20(5): 4587-4593, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702039

RESUMO

The purpose of the present study was to study the effects of resveratrol on cognitive function in rats with vascular dementia and to investigate the molecular mechanisms of its neuroprotective effects. Forty­five SD rats were randomly divided into 3 groups: The control group (Con group, n=15), the model group (VD group, n=15) and the resveratrol­treated VD group (Res group, n=15). The VD rats (the VD group and the Res group) were generated by bilateral common carotid artery occlusion. The rats in the Res group received daily resveratrol treatment intraperitoneally for 4 weeks. Cognitive function was tested using the Morris water maze test. The levels of SOD and MDA (oxidative stress indicators) were detected by ELISA kits. The protein expression of Bax, Bcl­2 and caspase­3 was detected by western blotting. Compared with the rats in the Con group, the rats in the VD group exhibited decreased cognitive function, significantly increased hippocampal content of MDA, Bax and caspase­3 (P<0.05), and significantly reduced hippocampal expression of SOD and Bcl­2 (P<0.05). Compared with the rats in the VD group, the rats in the Res group exhibited increased cognitive ability, reduced hippocampal content of MDA, Bax and caspase­3 (P<0.05), and increased hippocampal expression of SOD and Bcl­2 (P<0.05). Resveratrol treatment significantly improved the spatial learning and memory of the VD rats. The mechanism associated with the neuroprotective effects of resveratrol may be closely related to the inhibition of the apoptosis pathway and oxidative stress injury.


Assuntos
Demência Vascular/tratamento farmacológico , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Resveratrol/farmacologia , Animais , Caspase 3/metabolismo , Demência Vascular/patologia , Demência Vascular/fisiopatologia , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo
17.
Drug Des Devel Ther ; 13: 3669-3682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695334

RESUMO

Purpose: The lack of effective therapies mandates the development of new treatment strategies for vascular dementia (VaD). G protein-coupled receptor 124 (GPR124) may be a therapeutic target for angiogenesis-related diseases of CNS, including VaD. The GCPF peptide is a truncated and screened fragment of the GPR124 extracellular domain. The potential use of GCPF for VaD treatment, angiogenesis and targeting of integrin αvß3 are evaluated. Methods and results: First, the in vivo results indicated that the GCPF peptide could decrease mean escape latency and increase platform crossing times in BCCAO rats. Second, the in vitro and ex vivo results indicated that the GCPF peptide was an active angiogenic peptide and could promote hCMEC/D3 cell migration and adhesion to ECM molecules. Third, in silico analyses predicted that GCPF could specifically interact with integrin αvß3; the ∆G of GCPF binding to the binding pocket was -16.402 KJ/mol. The molecular characteristics indicated that highly hydrophilic GCPF with a pI of 11.70 had a short half-life in mammals (~1 hr). Finally, the ELISA experiments indicated that low dissociation constant (Kd= 2.412±0.455 nM) corresponds to the high affinity of GCPF for integrin αvß3. Conclusion: The data indicate that adhesion of GCPF immobilized on ECM surface to endothelial cells via integrin αvß3 modulates cellular functions to promote angiogenesis and improve cognitive function. This is the first report to prove that GCPF, a novel octapeptide, may be an effective strategy for VaD therapy.


Assuntos
Indutores da Angiogênese/farmacologia , Demência Vascular/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Receptores Acoplados a Proteínas-G/metabolismo , Indutores da Angiogênese/administração & dosagem , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Simulação por Computador , Demência Vascular/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Integrina alfaVbeta3/metabolismo , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley
18.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3423-3428, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602904

RESUMO

To investigate the effect of triptolide on cognitive dysfunction in vascular dementia rats and its effect on SIRT1/NF-κB pathway,fifty healthy male Sprague-Dawley rats were randomly divided into 5 groups: Sham operation group( Sham group),vascular dementia model group( 2 VO group),triptolide intraperitoneal injection group( TR group),triptolide intraperitoneal injection + EX527 intracerebroventricular administration group( T+E group),EX527 intracerebroventricular administration group( EX527 group). After 4 weeks of modeling,Morris water maze test and object recognition test were used to evaluate the learning and memory ability of rats. The morphological changes of hippocampus in each group were observed in brain tissue. The chemical colorimetry was used to detect the activities of SOD and MDA in hippocampus. IL-6 and TNF-α levels were detected by ELISA. Western blot was used to detect the expression of SIRT1,NF-κB,IκBα and caspase 3 in hippocampus. The results showed that compared with the Sham group,the learning and memory ability of the vascular dementia model rats was reduced,the SOD activity in the hippocampus was decreased,the MDA activity and IL-6 level were increased,the neuronal degeneration changed significantly,the expression of SIRT1 and IκBα was decreased and the expression of caspase 3 and NF-κB was significantly increased. After intervention by triptolide,the level of oxidative stress and the degenerative changes in hippocampus were significantly slowed down. The expression of SIRT1 and IκBα protein was increased and the expression of caspase 3 and NF-κB was significantly decreased. While,after intervention by triptolide and EX527,the expression of SIRT1 was decreased,the levels of oxidative stress and neuronal degeneration in the hippocampus were aggravated,and the learning and memory ability was reduced. The results showed that triptolide could improve cognitive impairment in vascular dementia rats and its mechanism may be related to SIRT1/NF-κB signaling pathway.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Diterpenos/farmacologia , NF-kappa B/metabolismo , Fenantrenos/farmacologia , Transdução de Sinais , Sirtuína 1/metabolismo , Animais , Compostos de Epóxi/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
19.
Biomed Pharmacother ; 120: 109492, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31593895

RESUMO

Vascular dementia (VD) is a degenerative cerebrovascular disorder, leading to progressive decline of cognitive abilities and memory. Rehmannioside A (ReA) is isolated from Rehmanniae Radix, which exhibits protective role against various diseases. The present study was performed to calculate the possible neuroprotective effects of ReA on VD. Here, the morris water maze (MWM) test and electrophysiological recordings indicated that ReA reduced cognitive deficits. Additionally, through hematoxylin and eosin (H&E) and Nissl staining, ReA attenuated the histological alterations of hippocampus in rats with VD. ReA group significantly reduced oxidative stress, inflammatory response and apoptosis in the hippocampus of rats with VD, which was linked to the activation of nuclear erythroid related factor-2 (Nrf2), while the inactivation of nuclear factor-κB (NF-κB) and Caspase-3. Further, the anti-oxidative, anti-inflammatory and anti-apoptosis abilities of ReA were confirmed in cells stimulated by hydrogen peroxide. Overall, the results above demonstrated the protective effects of ReA against cognitive deficits and indicated the potential value of ReA in the therapy of VD in future.


Assuntos
Apoptose/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Caspase 3/metabolismo , Cognição/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Demência Vascular/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
20.
Oxid Med Cell Longev ; 2019: 8416105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565154

RESUMO

Background: Astrogliosis can result in astrocytes with hypertrophic morphology after injury, indicated by extended processes and swollen cell bodies. Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily, has been reported to play a detrimental role in ischaemic brains and neurodegenerative diseases. Sailuotong (SLT) capsule is a standardized three-herb preparation composed of ginseng, ginkgo, and saffron for the treatment of vascular dementia. Although recent clinical trials have demonstrated the beneficial effect of SLT on vascular dementia, its potential cellular mechanism has not been fully explored. Methods: Male adult Sprague-Dawley (SD) rats were subjected to microsphere-embolized cerebral ischaemia. Immunostaining and Western blotting were performed to assess astrocytic reaction. Human astrocytes exposed to oxygen-glucose deprivation (OGD) were used to elucidate the effects of SLT-induced inflammation and astrocytic reaction. Results: A memory recovery effect was found to be associated with the cerebral ischaemia-induced expression of inflammatory proteins and the suppression of LCN2 expression in the brain. Additionally, SLT reduced the astrocytic reaction, LCN2 expression, and the phosphorylation of STAT3 and JAK2. For in vitro experiments, OGD-induced expression of inflammation and LCN2 was also decreased in human astrocyte by the SLT treatment. Moreover, LCN2 overexpression significantly enhanced the above effects. SLT downregulated these effects that were enhanced by LCN2 overexpression. Conclusions: SLT mediates neuroinflammation, thereby protecting against ischaemic brain injury by inhibiting astrogliosis and suppressing neuroinflammation via the LCN2-JAK2/STAT3 pathway, providing a new idea for the treatment strategy of ischaemic stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Lipocalina-2/antagonistas & inibidores , Lipocalina-2/metabolismo , Memória/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Transfecção
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