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1.
J Pharm Biomed Anal ; 183: 113143, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045824

RESUMO

Sphaeralcea angustifolia (Cav.) G. Don (Malvaceae) is a plant used in inflammatory illnesses. The scopoletin was the main responsible compound for the anti-arthritic effect in this species. The therapeutic effectiveness of a S. angustifolia dichloromethane extract gel standardized in scopoletin was confirmed in patients with osteoarthritis. Cells in suspension cultures from S. angustifolia were established for scopoletin production; in addition, tomentin, and sphaeralcic acid compounds were isolated from this culture. Tomentin and sphaeralcic acid showed also anti-inflammatory and immunomodulatory effects. Validation of HPLC quantification methods for sphaeralcic acid, and scopoletin and tomentin was performed in addition to extraction efficiency and stability of the active compounds. The pharmacokinetic parameters of scopoletin and tomentine in mixture, and sphaeralcic acid after oral administration of standardized active fraction indicated that these compounds followed a two-compartment model; they were bioavailable in plasma (absorbed) and distributed to blank organs. No products derived from their biotransformation were detected. The objective of this work was to determine the pharmacokinetic constants of urinary and fecal elimination in mice of the anti-arthritic compounds, after oral administration (400 mg / kg) of a standardized active fraction (SaTES) of S. angustifolia. It was established that the coumarin mixture (scopoletin and tomentin) were eliminated by the urine; while, sphaeralcic acid was mainly eliminated by fecal path, following both a non-compartmental behavior. No products derived from their biotransformation were detected.

2.
Biomed Pharmacother ; 118: 109349, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545221

RESUMO

Neuroinflammation, a centralized immune response, is a physiological process by which the organism attempts to remove an injurious stimulus in the central nervous system. Nonetheless, it is known that chronic inflammatory processes play an important role in the onset and progression of neurodegenerative disorders, such as Alzheimer´s disease (AD). Based on this, new strategies to treat AD have been proposed. Among them, the use of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of this disease. Unfortunately, the prolonged use of NSAIDs results in adverse secondary effects. In this context, plants secondary metabolites have become of great interest. Particularly, our group has demonstrated that the hydroalcoholic extract of Malva parviflora (MpHA) has anti-inflammatory effect and is capable of improving the cognitive deficit present in an AD model. To further characterize the Malva parviflora compounds with anti-inflammatory properties, here we generated a fraction from a dichloromethane extract, which constitutes a less complex mix of compounds than the MpHA. This approach allowed us to isolate a fraction (MpF10) with anti-inflammatory activity, able to ameliorate the spatial learning and memory impairment, and to reduce both astrogliosis as well as IL-1ß and TNF production in a murine model of LPS-mediated neuroinflammation. Among the identified compounds in the MpF10, we found daucosterol (MpDau), which prevented LPS-induced neuroinflammation. Interestingly, MpF10 and MpDau inhibit NFκB activity in macrophages exposed to LPS. Therefore, we propose that the compounds present in the MpF10 represent an alternative to treat neuroinflammation, an important process developed during neurodegenerative diseases such as AD.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31428176

RESUMO

Background: Galphimia glauca has been used for many years in Mexican Traditional Medicine to calm "insane people." Triterpenes, known as galphimines, were identified in this species. One of them, Galphimine-B (G-B), acts selectively on dopaminergic neurons by antagonizing the effect of glutamate on NMDA receptors. The objective of this study was to evaluate the effect of G. glauca methanolic extract (GgMeOH), a Galphimine-Rich Fraction (GRF), as well as the galphimines G-A, G-B, and G-E, on the acute psychosis induced by Apomorphine (APO) in mice and on schizophrenia-like symptoms induced by subchronic administration of MK-801. Method: On the first day, ICR male mice were given GgMeOH, GRF, or one of the galphimines. On day two, animals were treated with APO, and on day 3, they were subjected to behavioral tests. In a second test, MK-801 was administered daily for 28 days. In this case, animals were treated daily with G. glauca products from day 9 to day 28 and then subjected to behavioral tests (passive avoidance test, open field test, forced swimming test, and social interaction test). Results: The increased number of stereotyped behaviors and grooming behaviors induced with APO were counteracted by all of the experimental treatments. MK-801 induced an increase in immobility time, which was blocked with G-B; GRF counteracted the decreased social interaction, and GgMeOH and GRF prevented the memory loss induced by MK-801. Conclusion: G. glauca and their derivatives products (GRF and galphimines) were able to interact with the dopaminergic and glutamatergic drugs and to block different behaviors associated with some of the positive, negative, and cognitive symptoms of induced schizophrenia in mice. It is necessary to continue with this research, in order to identify their mechanism of action.

4.
Med Princ Pract ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31466071

RESUMO

OBJECTIVE: To evaluate the antidepressant effect of Bauhinia blakeana and a standardized fraction in the forced swimming test on mice with neuro-inflammation induced with lipopolysaccharides (LPS). MATERIALS AND METHODS: Evaluation of the antidepressant effect of Bauhinia blakeana hydroalcoholic extract (BbHA) and its fractions was carried out in behavioral tests on mice with lipopolysaccharide (LPS)-induced neuroinflammation. RESULTS: BbHA had a significant antidepressant effect, measured on healthy mice in the forced swimming test (FST). Bio-guided chemical separation of the extract produced a methanolic fraction (BbMe), which decreased the immobility time in FST. In this test, the intraperitoneal administration of LPS induced depression in mice, and BbHA and BbMe counteracted this effect, significantly decreasing the induced depression. Quantification of inflammatory mediators (IL-10, IL-4, IL-6, IL-1ß, and TNF-α) in the brain demonstrated that BbHA and BbMe effectively decreased the effect of LPS on the brain concentration of all measured cytokines. CONCLUSIONS: Bauhinia blakeana produced an antidepressant effect, while BbMe also exerted a modulating effect, on the damage induced by LPS. Rutin, a glycosylated flavonoid, was identified as the main compound in the active fraction, which could mediate in the antidepressant and immunomodulatory effect.

5.
J Neuroinflammation ; 16(1): 143, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291963

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a neuropathology strongly associated with the activation of inflammatory pathways. Accordingly, inflammation resulting from obesity exacerbates learning and memory deficits in humans and in animal models of AD. Consequently, the long-term use of non-steroidal anti-inflammatory agents diminishes the risk for developing AD, but the side effects produced by these drugs limit their prophylactic use. Thus, plants natural products have become an excellent option for modern therapeutics. Malva parviflora is a plant well known for its anti-inflammatory properties. METHODS: The present study was aimed to determine the anti-inflammatory potential of M. parviflora leaf hydroalcoholic extract (MpHE) on AD pathology in lean and obese transgenic 5XFAD mice, a model of familial AD. The inflammatory response and Amyloid ß (Aß) plaque load in lean and obese 5XFAD mice untreated or treated with MpHE was evaluated by immunolocalization (Iba-1 and GFAP) and RT-qPCR (TNF) assays and thioflavin-S staining, respectively. Spatial learning memory was assessed by the Morris Water Maze behavioral test. Microglia phagocytosis capacity was analyzed in vivo and by ex vivo and in vitro assays, and its activation by morphological changes (phalloidin staining) and expression of CD86, Mgl1, and TREM-2 by RT-qPCR. The mechanism triggered by the MpHE was characterized in microglia primary cultures and ex vivo assays by immunoblot (PPAR-γ) and RT-qPCR (CD36) and in vivo by flow cytometry, using GW9662 (PPAR-γ inhibitor) and pioglitazone (PPAR-γ agonist). The presence of bioactive compounds in the MpHE was determined by HPLC. RESULTS: MpHE efficiently reduced astrogliosis, the presence of insoluble Aß peptides in the hippocampus and spatial learning impairments, of both, lean, and obese 5XFAD mice. This was accompanied by microglial cells accumulation around Aß plaques in the cortex and the hippocampus and decreased expression of M1 inflammatory markers. Consistent with the fact that the MpHE rescued microglia phagocytic capacity via a PPAR-γ/CD36-dependent mechanism, the MpHE possess oleanolic acid and scopoletin as active phytochemicals. CONCLUSIONS: M. parviflora suppresses neuroinflammation by inhibiting microglia pro-inflammatory M1 phenotype and promoting microglia phagocytosis. Therefore, M. parviflora phytochemicals represent an alternative to prevent cognitive impairment associated with a metabolic disorder as well as an effective prophylactic candidate for AD progression.


Assuntos
Doença de Alzheimer , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/patologia , Microglia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/patologia , Disfunção Cognitiva/etiologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Malva , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , PPAR gama/metabolismo , Fagocitose/efeitos dos fármacos , Folhas de Planta
6.
Nat Prod Res ; : 1-4, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31084220

RESUMO

Chronic neuroinflammation is a key component of many neurodegenerative disorders. Chronic activation of this process produces pro-inflammatory cytokines, prostaglandins and reactive oxygen species that induce brain injury and neuronal dysfunction. Agave species contain saponins, compounds with anti-inflammatory activity. Extracts from A. tequilana (At), A. angustifolia (Aan), A. Americana (Aam) (125 mg/kg) and cantalasaponin-1 (5 and 10 mg/kg, isolated from Aam) were administered to male ICR mice with lipopolysaccharide (LPS)-induced neuroinflammation, after which inflammatory cytokines were measured in brain homogenates by using an enzyme-linked immunoassay (ELISA) test. All agave extracts and cantalasaponin-1, reduced brain concentration of LPS-induced pro-inflammatory cytokines IL-6 and TNF-α. Moreover, Cantalasaponin-1 increased the brain concentration of the anti-inflammatory cytokine IL-10. Agave extracts and derived compounds show promising results in the development of novel drugs for neuroinflammatory disease therapy.

7.
Biomed Res Int ; 2019: 1037036, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834253

RESUMO

Galphimine-B (G-B), a compound isolated from Galphimia glauca, has been shown to possess important anxiolytic activity. In this study, we evaluated the effectiveness and tolerability of a G-B standardized extract (experimental treatment) that was administered daily for 10 weeks in patients with moderate or severe Generalized Anxiety Disorder (GAD). Alprazolam was used as control treatment and administered under the same conditions. A total of 167 patients were included. At the start of the study, the severe anxiety condition prevailed, with an average on the Hamilton Anxiety Scale of 35.1 ± 8.8 and 35.8 ± 8.1 points in the control and experimental groups, respectively. After the 10 weeks of administration, the average was reduced in the control group to 4.6 ± 6.5 points and in the experimental group to 3.5 ± 5.5 points. Therapeutic success in the control group was 85.7% and in the experimental group, 92.0%. A high proportion of patients (22.2%) treated with Alprazolam manifested daytime sleepiness, while in the group treated with the G-B standardized extract, daytime sleepiness was found in 4.7%. In conclusion, a G-B standardized extract demonstrated therapeutic effectiveness in patients with GAD, without exhibiting significant difference with Alprazolam, but showing fewer cases of daytime sleepiness. The trial was registered at http://clinicaltrials.gov by identifier: NCT03702803.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Galphimia/química , Extratos Vegetais/administração & dosagem , Triterpenos/administração & dosagem , Alprazolam/administração & dosagem , Transtornos de Ansiedade/patologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente/normas , Extratos Vegetais/química , Triterpenos/química
8.
Biol Pharm Bull ; 42(2): 201-211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30713252

RESUMO

The main objective of treatment against hypertension is not only to reduce blood pressure levels, but also to reduce vascular risk in general. In the present work, administering angiotensin II (AGII; 0.2 µg/kg intraperitoneally (i.p.) for 12 weeks) activates the hypothalamic-pituitary-adrenal (HPA) axis, which caused an increase in corticosterone levels, as well as in proinflammatory cytokines (interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α)) and macrophage chemotactic protein 1 (MCP-1), and decreased anti-inflammatory cytokines (interleukin 10 (IL-10) and interleukin 4 (IL-4)). On observing the behavior in the different models, an anxiogenic effect (elevated plus maze (EPM)) and cognitive impairment (water Morris maze (WMM)) was observed in animals with AGII. By administering organic extracts from Ocimum basilicum (Oba-EtOAc) and Ocimum selloi (Ose-EtOAc), and some doses of rosmarinic acid (RA) (6 weeks per os (p.o.)), the damage caused by AGII was stopped by re-establishing corticosterone serum levels and by decreasing the proinflammatory cytokines and MCP-1.


Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Hipertensão/tratamento farmacológico , Ocimum/química , Extratos Vegetais/farmacologia , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Corticosterona/sangue , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos ICR , Ocimum basilicum/química , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Distribuição Aleatória , Navegação Espacial/efeitos dos fármacos
9.
Biol Pharm Bull ; 42(1): 18-25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30606987

RESUMO

Hypertension is a disease of high prevalence and morbidity where vascular inflammation and associated oxidative stress (endothelial dysfunction) is the underlying cause of this pathology. We are reporting the antihypertensive activity of extracts and fractions of Malva parviflora in mice with chronic and acute hypertension. Also, the treatments of this plant were able to counteract the kidney inflammation and associated oxidative stress. The chronic hypertension model consisted of administration of angiotensin II (AGII) during 12 weeks, causing a sustained increase in systolic (SBP) or diastolic (DBP) pressure, with values of pharmacological constants of: ED50 = 0.038 mg/kg y Emax = 135 mmHg for SBP and ED50 = 0.046 mg/kg y Emax = 98 mmHg for DBP. The chronic hypertension caused the inflammation and lipid peroxidation in kidneys, measured by of tissue level of cytokines such as interleukin-1ß (IL-1ß), IL-6, Tumor Necrosis Factor-α (TNF-α), IL-10 and malondialdehyde, and treatments for M. parviflora were able to modulate these parameters. The chemical fractionation allowed to identify three compounds: oleanolic acid, tiliroside and scopoletin, which were tested in a model of acute hypertension. The pharmacodynamic parameters for SBP were ED50 = 0.01 and 0.12 mg/kg while Emax = 33.22 and 37.74 mmHg for scopoletin and tiliroside, respectively; whereas that for DBP data were ED50 = 0.01 and 0.02 mg/kg; with an Emax = 7.00 and 6.24 mmHg, in the same order. M. parviflora, is able to counteract the effect of chronic and acute administration of AGII, on hypertension, but also the inflammatory and oxidative damage in the kidney. The oleanolic acid, scopoletin and tiliroside are the compounds responsible for such activities.


Assuntos
Anti-Hipertensivos/uso terapêutico , Flavonoides/uso terapêutico , Hipertensão/tratamento farmacológico , Malva , Extratos Vegetais/uso terapêutico , Escopoletina/uso terapêutico , Angiotensina II/toxicidade , Animais , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Relação Dose-Resposta a Droga , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Hipertensão/sangue , Hipertensão/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Escopoletina/isolamento & purificação , Escopoletina/farmacologia
10.
Acta Neurochir (Wien) ; 160(12): 2489-2500, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30413938

RESUMO

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective technique to help to locate and to delimit the epileptogenic area and/or to define relationships with functional cortical areas. We intend to describe the surgical technique and verify the accuracy, safety, and effectiveness of robot-assisted SEEG in a newly created SEEG program in a pediatric center. We focus on the technical difficulties encountered at the early stages of this program. METHODS: We prospectively collected SEEG indication, intraoperative events, accuracy calculated by fusion of postoperative CT with preoperative planning, complications, and usefulness of SEEG in terms of answering preimplantation hypothesis. RESULTS: Fourteen patients between the ages of 5 and 18 years old (mean 10 years) with drug-resistant epilepsy were operated on between April 2016 and April 2018. One hundred sixty-four electrodes were implanted in total. The median entry point localization error (EPLE) was 1.57 mm (1-2.25 mm) and the median target point localization error (TPLE) was 1.77 mm (1.2-2.6 mm). We recorded seven intraoperative technical issues. Two patients suffered complications: meningitis without demonstrated germ in one patient and a right frontal hematoma in the other. In all cases, the SEEG was useful for the therapeutic decision-making. CONCLUSION: SEEG has been useful for decision-making in all our pediatric patients. The robotic arm is an accurate tool for the insertion of the deep electrodes. Nevertheless, it is an invasive technique not risk-free and many problems can appear at the beginning of a robotic arm-assisted SEEG program that must be taken into account beforehand.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/métodos , Complicações Pós-Operatórias/epidemiologia , Robótica/métodos , Técnicas Estereotáxicas/efeitos adversos , Adolescente , Criança , Pré-Escolar , Tomada de Decisão Clínica , Epilepsia Resistente a Medicamentos/diagnóstico , Eletrodos Implantados/efeitos adversos , Eletrodos Implantados/normas , Eletroencefalografia/efeitos adversos , Eletroencefalografia/instrumentação , Eletroencefalografia/normas , Feminino , Humanos , Masculino , Robótica/instrumentação , Robótica/normas , Técnicas Estereotáxicas/instrumentação , Técnicas Estereotáxicas/normas
11.
J Neurosurg Pediatr ; 22(4): 416-425, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30028274

RESUMO

OBJECTIVE: The purpose of this study was to verify the safety and accuracy of the Neuromate stereotactic robot for use in deep brain stimulation (DBS) electrode implantation for the treatment of hyperkinetic movement disorders in childhood and describe the authors' initial clinical results. METHODS: A prospective evaluation of pediatric patients with dystonia and other hyperkinetic movement disorders was carried out during the 1st year after the start-up of a pediatric DBS unit in Barcelona. Electrodes were implanted bilaterally in the globus pallidus internus (GPi) using the Neuromate robot without the stereotactic frame. The authors calculated the distances between the electrodes and their respective planned trajectories, merging the postoperative CT with the preoperative plan using VoXim software. Clinical outcome was monitored using validated scales for dystonia and myoclonus preoperatively and at 1 month and 6 months postoperatively and by means of a quality-of-life questionnaire for children, administered before surgery and at 6 months' follow-up. We also recorded complications derived from the implantation technique, "hardware," and stimulation. RESULTS: Six patients aged 7 to 16 years and diagnosed with isolated dystonia ( DYT1 negative) (3 patients), choreo-dystonia related to PDE2A mutation (1 patient), or myoclonus-dystonia syndrome SGCE mutations (2 patients) were evaluated during a period of 6 to 19 months. The average accuracy in the placement of the electrodes was 1.24 mm at the target point. At the 6-month follow-up, patients showed an improvement in the motor (65%) and functional (48%) components of the Burke-Fahn-Marsden Dystonia Rating Scale. Patients with myoclonus and SGCE mutations also showed an improvement in action myoclonus (95%-100%) and in functional tests (50%-75%) according to the Unified Motor-Rating Scale. The Neuro-QOL score revealed inconsistent results, with improvement in motor function and social relationships but worsening in anxiety, cognitive function, and pain. The only surgical complication was medial displacement of the first electrode, which limited intensity of stimulation in the lower contacts, in one case. CONCLUSIONS: The Neuromate stereotactic robot is an accurate and safe tool for the placement of GPi electrodes in children with hyperkinetic movement disorders.


Assuntos
Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Transtornos dos Movimentos/terapia , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Adolescente , Criança , Feminino , Globo Pálido/fisiopatologia , Globo Pálido/cirurgia , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
12.
Biomed Pharmacother ; 103: 879-888, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29710504

RESUMO

Due to the high prevalence of psychiatric disorders and the prevalent side effects produced by the antipsychotic drugs available, it is necessary to search for new therapeutic options. Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases. From this plant, some compounds, denominated galphimines, have been discovered and have shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the Ventral tegmental area. The objective of the present work was to evaluate the effect produced by the G. glauca extract, a Galphimine rich fraction (GRF), as well as the pure galphimines (G-A, G-B, and G-E) on behavioral models in mice. Products obtained from G. glauca were evaluated in the Haloperidol-induced catalepsy test and in the acute schizophrenia-like symptoms-induced with Ketamine (KET) in mice. Catalepsy was evaluated through the bar test, and schizophrenia-like symptoms, by means of the Open Field Test (OFT), Passive Avoidance Test (PAT), and the Forced Swimming Test (FST). The methanolic extract from G. glauca, GRF, and the pure galphimines were able to interact with the dopaminergic pathway and modify the behavioral response such as to potentiate the cataleptic effect induced with Haloperidol and to inhibit the behavior induced by KET in mice exposed to OFT, and FST. Moreover, the G. glauca extract and GRF were capable of blocking the cognitive decline that was induced with KET in mice (evaluated by PAT). Based on these results, it is possible to assume that part of the effect of G. glauca is due to the interaction of Galphimines with the dopaminergic and glutamatergic systems in vivo. It can be concluded that the products obtained from G. glauca potentiate the cataleptic effect induced with Haloperidol and show a protector effect on some of the symptoms generated by KET in mice (KET is capable of provoking halucinations in humans and psychosis-like behaviour in mice). With this basis, the metanolic extract from G. glauca, and the GRF are capable of blocking positive and cognitive symptoms associated with psychosis induced by KET. In addition, it could be suggested that the galphimines are responsible for the inhibition of the positive symptoms observed.


Assuntos
Antipsicóticos/efeitos adversos , Catalepsia/induzido quimicamente , Galphimia/efeitos adversos , Haloperidol/efeitos adversos , Ketamina/efeitos adversos , Extratos Vegetais/efeitos adversos , Triterpenos/efeitos adversos , Animais , Antipsicóticos/administração & dosagem , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Catalepsia/psicologia , Relação Dose-Resposta a Droga , Haloperidol/administração & dosagem , Interações Ervas-Drogas , Ketamina/administração & dosagem , Masculino , Camundongos Endogâmicos ICR , Extratos Vegetais/administração & dosagem , Natação , Triterpenos/administração & dosagem
13.
Nutrients ; 10(3)2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29495578

RESUMO

Inflammation and oxidative stress play major roles in endothelial dysfunction, and are key factors in the progression of cardiovascular diseases. The aim of this study was to evaluate in vitro the effect of three subfractions (SFs) from the Cucumis sativus aqueous fraction to reduce inflammatory factors and oxidative stress induced by angiotensin II (Ang II) in human microvascular endothelial cells-1 (HMEC-1) cells. The cells were cultured with different concentrations of Ang II and 0.08 or 10 µg/mL of SF1, SF2, or SF3, or 10 µmol of losartan as a control. IL-6 (Interleukin 6) concentration was quantified. To identify the most effective SF combinations, HMEC-1 cells were cultured as described above in the presence of four combinations of SF1 and SF3. Then, the effects of the most effective combination on the expression of adhesion molecules, the production of reactive oxygen species (ROS), and the bioavailability of nitric oxide (NO) were evaluated. Finally, a mass spectrometry analysis was performed. Both SF1 and SF3 subfractions decreased the induction of IL-6 by Ang II, and C4 (SF1 and SF3, 10 µg/mL each) was the most effective combination to inhibit the production of IL-6. Additionally, C4 prevented the expression of adhesion molecules, reduced the production of ROS, and increased the bioavailability of NO. Glycine, arginine, asparagine, lysine, and aspartic acid were the main components of both subfractions. These results demonstrate that C4 has anti-inflammatory and antioxidant effects.


Assuntos
Aminoácidos/farmacologia , Angiotensina II/toxicidade , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cucumis sativus , Células Endoteliais/efeitos dos fármacos , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Aminoácidos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Cucumis sativus/química , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Óxido Nítrico/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Espécies Reativas de Oxigênio/metabolismo
14.
Biomed Pharmacother ; 96: 320-327, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29017144

RESUMO

Aloysia triphylla (Verbenaceae) is an aromatic medicinal plant, and it is used for the treatment of "nervous" problems as, "sadness" and "nervousness". While, there are no reports about its pharmacological activity in animal models. The objective of this work was to evaluate the anxiolytic effect of the extracts and fractions of this species and to measure the interaction of the most active fraction with serotonergic, glutamatergic and GABAergic drugs. An elevated plus maze test was carried ought where the methanol (AtM), dicloromethane (AtD) and hexanic (AtH) extracts presented anxiolytic activity in mice when exposed to the test. Also, different fractions obtained from the AtD were evaluated (AtF1, AtF2 and AtF3, 15mg/kg), and showed that fraction AtF1 possessed the anxiolytic activity, in the same model. Then, AtF1 was co-administered with different drugs, which act on GABAergic (bicuculline, picrotoxin, pentylenetetrazol, baclofen and phaclofen), or serotononinergic (DOI, 8-OH-DPAT, WAY 100635 and ketanserine) or glutamatergic (NMDA, MPEP and MK-801) systems. The anxiolytic activity of AtF1 was modified by GABAergic and serotoninergic drugs. Chemical analysis of this fraction by using GC-MS, showed that it contains hexadecanoic acid, hexadecanoic acid methyl ester, octadecanoic acid methyl ester, eicosanoic acid methyl ester, vitamin E, α-amiryn, campesterol, sitosterol, stigmastan-2,22, dien-3-ol (4) and stigmasta 5, 24 (28) dien-3-ol.


Assuntos
Ansiolíticos/farmacologia , Fármacos atuantes sobre Aminoácidos Excitatórios/farmacologia , Ácidos Graxos/farmacologia , GABAérgicos/farmacologia , Serotoninérgicos/farmacologia , Terpenos/farmacologia , Verbenaceae , Animais , Ansiolíticos/isolamento & purificação , Fármacos atuantes sobre Aminoácidos Excitatórios/isolamento & purificação , Ácidos Graxos/isolamento & purificação , GABAérgicos/isolamento & purificação , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta , Caules de Planta , Serotoninérgicos/isolamento & purificação , Terpenos/isolamento & purificação
15.
Rev. neurol. (Ed. impr.) ; 65(3): 112-116, 1 ago., 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-165554

RESUMO

Introducción. La trisomía 9 es una cromosomopatía inusual en pacientes nacidos vivos, que frecuentemente se acompaña de anomalías funcionales y estructurales del sistema nervioso central. Entre otras muchas alteraciones, varios trabajos en la bibliografía anglosajona demuestran una asociación entre cromosomopatía 9 y patología de los plexos coroideos. Caso clínico. Varón de 4 meses de vida con mosaicismo de trisomía 9 asociado a hidrocefalia secundaria a hiperplasia de los plexos coroideos, que fue remitido por clínica de hipertensión intracraneal. El procedimiento derivativo de líquido cefalorraquídeo por el que optamos inicialmente provocó una ascitis masiva debida a la producción desmesurada de líquido cefalorraquídeo, y desembocó en una cascada de múltiples intervenciones quirúrgicas, entre las que se incluyeron procedimientos endoscópicos y derivativos. Conclusiones. Se trata de un ejemplo más de asociación entre patología de los plexos coroideos y cromosomopatía 9. Debido a su escasa incidencia, es difícil establecer el diagnóstico de hidrocefalia secundaria a hiperplasia de los plexos y, por tanto, el tratamiento más adecuado. En este tipo de hidrocefalia existe un doble mecanismo fisiopatológico, que implica un aumento de producción de líquido cefalorraquídeo y una disminución de su reabsorción. A pesar de tener en cuenta dicha consideración, el tratamiento de la hidrocefalia secundaria a hiperplasia de los plexos supone un verdadero reto que habitualmente pasa por múltiples procedimientos quirúrgicos, desde la plexectomía o coagulación de los plexos coroideos hasta la implantación de dispositivos de derivación de líquido cefalorraquídeo (AU)


Introduction. Trisomy 9 is an unusual chromosome abnormality in live-born patients, which is frequently accompanied by functional and structural anomalies of the central nervous system. Among many other alterations, several studies have been published in the English-speaking literature that show an association between chromosome 9 abnormality and pathologies affecting the choroid plexuses. Case report. We report the case of a 4-month-old male with trisomy 9 mosaicism associated to hydrocephalus secondary to choroid plexus hyperplasia, who was referred due to a clinical picture of intracranial hypertension. The cerebrospinal fluid (CSF) drainage procedure that was initially chosen caused massive ascites due to an excessive production of CSF, and led to a cascade of multiple surgical interventions, which included endoscopic and drainage procedures. Conclusions. This is another example of an association between choroid plexus pathologies and chromosome 9 abnormality. Due to its scarce incidence, diagnosis of hydrocephalus secondary to plexus hyperplasia is difficult, as is selecting its most suitable treatment. In this type of hydrocephalus there is a double pathophysiological mechanism, which involves an increase in CSF production and a decrease in its reabsorption. Despite taking these considerations into account, the treatment of hydrocephalus secondary to plexus hyperplasia is a real challenge that usually leads to multiple surgical interventions ranging from plexectomy or coagulation of the choroid plexuses to the implantation of CSF drainage devices (AU)


Assuntos
Humanos , Masculino , Lactente , Hidrocefalia/etiologia , Neoplasias do Plexo Corióideo/complicações , Trissomia/genética , Derivações do Líquido Cefalorraquidiano/métodos , Mosaicismo , Procedimentos Neurocirúrgicos/métodos
16.
Neurol India ; 65(4): 808-813, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28681757

RESUMO

Chordoid glioma (CG) of the third ventricle is an unusual neoplasm of glial nature, which is almost exclusively located in the anterior wall of the third ventricle, in close relation with the hypothalamus. Magnetic resonance images show CG as a suprasellar, hypo- to isointense mass, homogeneously enhancing after the administration of gadolinium. Since its description in 1998 by Brat et al., approximately 85 cases have been reported. Some of its pathological features are under discussion and its histological origin still remains unclear. In this study, we present a patient having this rare entity. We review the management of CG reported in literature. We also studied its pathological features, the postoperative mortality and morbidity related to radical surgical resection, and the implemented adjuvant therapies. Due to its classical clinical features and its close resemblance to other lesions in the region, it is an entity unlikely to be suspected prior to its histological diagnosis. Despite the benign nature of this tumor, the clinical outcome might be poor. Its treatment may represent a real challenge because it involves critical anatomical areas, leading to high postoperative morbidity and mortality rates. An initial minimally invasive management and adjuvant therapies, such as radiosurgery, in case of symptomatic recurrences, can be effective handling strategies.


Assuntos
Neoplasias do Ventrículo Cerebral/terapia , Glioma/terapia , Terceiro Ventrículo , Neoplasias do Ventrículo Cerebral/patologia , Neoplasias do Ventrículo Cerebral/cirurgia , Terapia Combinada , Gerenciamento Clínico , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Síndrome das Pernas Inquietas/etiologia , Resultado do Tratamento
17.
Molecules ; 22(8)2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28749448

RESUMO

An anxiolytic fraction of Tilia americana standardized in tiliroside, rutin, quercitrin, quercetin glucoside, and kaempferol was obtained. After oral administration of the fraction, the above-mentioned flavonoids were not detected in plasma over 24 h. However, meta and para hydroxyphenylacetic acid and dihydroxyphenylacetic acid (m-HPAA, p-HPAA and DOPAC) were monitored. These are the biotransformation compounds of the aglycones of kaempferol and quercetin; these aglycones are products of the other flavonoids present in the anxiolytic fraction. The analytical methods (HPLC) for flavonoids and the related compounds (m-HPAA, p-HPAA and DOPAC) were validated, determining the parameters of accuracy, precision, specificity or selectivity, limit of detection, quantification range, and robustness. The pharmacokinetic assay was performed with ICR mice strains, which were given 200 mg/kg of the standardized active fraction. The results of validation of the analytical methods were obtained, allowing it to be established in a validated way that no flavonoids present in the anxiolytic fraction of T. americana were detected in plasma. However, detection and follow up was possible for the serum levels of m-HPAA, p-HPAA, and DOPAC. The three compounds follow a two-compartment model with very similar parameters between m-HPAA and p-HPAA, some being different from the ones characterized in the pharmacokinetics of DOPAC.


Assuntos
Ansiolíticos/farmacocinética , Extratos Vegetais/farmacocinética , Tilia/química , Administração Oral , Análise de Variância , Animais , Ansiolíticos/administração & dosagem , Biotransformação , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Flavonoides/sangue , Flavonoides/química , Camundongos Endogâmicos ICR , Extratos Vegetais/administração & dosagem , Padrões de Referência
18.
Molecules ; 22(6)2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28587079

RESUMO

In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1ß, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana, provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1ß, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: ß-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.


Assuntos
Agave/química , Autoimunidade/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Extratos Vegetais/farmacologia , Terpenos/efeitos adversos , Animais , Autoanticorpos/sangue , Autoanticorpos/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/imunologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos BALB C
19.
Molecules ; 22(6)2017 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-28587132

RESUMO

The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions showed activity within a range of 67-89%. Due to the fact F-14 showed the highest effect, it was separated, yielding a proanthocyanidin-type called epicatechin-(4ß â†’ 8)-epicatechin-(4ß â†’ 8, 2ß â†’ O → 7) epicatechin (ETP). This compound (2.0 mg/ear) provoked 72% of edema inhibition (ED50 = 0.25 mg/ear, Emax = 52.9%). After 9 days of treatment, joint inflammation was decreasing, and on the last day, SsEtOAc (400 mg/kg), F-14 and ETP (10 mg/kg), SsEtOAc (200 mg/kg), methotrexate (MTX) 1.0 mg/kg and meloxicam (MEL) 1.5 mg/kg, produced an inhibition articulate edema of 94, 62, 36, 21, 80, and 54%, respectively. In the joint, pro-inflammatory molecules were elevated in animals without treatment (vehicle group, VEH). Treatments from S. schiedeana induced a decrease in the concentration of interleukin (IL)-1ß, IL-17, and IL-6, and SsEtOAc at a higher dose diminished tumor necrosis factor (TNF-α). IL-10 and IL-4 were fewer in the VEH group in comparison with healthy mice; the animals with treatments from S. schiedeana induced an increment in the levels of these cytokines in joint and spleen.


Assuntos
Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Polímeros , Proantocianidinas/farmacologia , Sapindaceae/química , Animais , Anti-Inflamatórios/química , Artrite/tratamento farmacológico , Artrite/metabolismo , Artrite/patologia , Citocinas/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Feminino , Mediadores da Inflamação/metabolismo , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Proantocianidinas/química
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