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1.
J Chromatogr A ; 1617: 460834, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31916986

RESUMO

Sertraline is an antidepressant in a group of drugs called selective serotonin reuptake inhibitors. Four stereoisomeric compounds would be produced in its synthetic preparation due to two chiral carbons on its chemical structures. In the present work, stereoselective liquid-liquid extraction of isomeric sertraline with substituted cyclodextrins as stereoselective extractant was investigated. Factors affecting the distribution performance, including organic solvents, types of extractants, pH value, buffer solution of aqueous phase, concentration of extractant and temperature, were investigated. Under optimized conditions, a stereoselectivity of 1.404 was obtained for cis-sertraline and a stereoselectivity of 2.373 was obtained for trans-sertraline when hydroxypropyl-ß-cyclodextrin was used as the stereoselective extractant, and a stereoselectivity of 1.685 was achieved for trans-sertraline with methyl-ß-cyclodextrin as extractant. An unusual stereoselective combination was observed for trans-sertraline and cis-sertraline when sodium carbonate buffer was used. Successful stereoselective separation of trans-sertraline and cis-sertraline, (1S, 4R) and (1R, 4S)-sertraline by analytical countercurrent chromatography with methyl-ß-cyclodextrin as stereoselective selector was achieved, using a biphasic solvent system composed of n-hexane : 0.1 mol L-1 citrate buffer solution with pH7.6 (1:1, v/v).


Assuntos
Antidepressivos/química , Distribuição Contracorrente/métodos , Inibidores de Captação de Serotonina/química , Sertralina/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Antidepressivos/isolamento & purificação , Ciclodextrinas/química , Extração Líquido-Líquido , Inibidores de Captação de Serotonina/isolamento & purificação , Sertralina/isolamento & purificação , Solventes , Estereoisomerismo , beta-Ciclodextrinas/química
2.
Nat Prod Res ; 34(6): 868-871, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30417675

RESUMO

The present study explored the antidepressant-like activity of α-mangostin (α-MG) and the possible mechanism in this process in the tail suspension test (TST) in mice. The results revealed that α-MG (5 mg/kg, i.p.) exhibited markedly antidepressant-like activity, which could be reversed by pretreatment with haloperidol (a non-selective D2 receptor antagonist), bicuculline (a competitive GABA antagonist), p-chlorophenylalanine (an inhibitor of 5-HT synthesis). Meanwhile, α-MG also effectively increased the brain DA, 5-HT and GABA levels in mice exposed to TST, indicating that the antidepressant-like effect of α-MG might be mediated by the GABAergic, serotonergic and dopaminergic systems.[Formula: see text].


Assuntos
Antidepressivos/isolamento & purificação , Dopamina/metabolismo , Serotonina/metabolismo , Xantonas/farmacologia , Ácido gama-Aminobutírico/metabolismo , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Depressão/tratamento farmacológico , Camundongos , Xantonas/uso terapêutico
3.
Bioanalysis ; 12(1): 35-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31849264

RESUMO

Aim: Routine therapeutic drug monitoring is highly recommended since common antidepressant combinations increase the risk of drug-drug interactions or overlapping toxicity. Materials & methods: A magnetic solid-phase extraction by using C18-functionalized magnetic silica nanoparticles (C18-Fe3O4@SiO2 NPs) as sorbent was proposed for rapid extraction of venlafaxine, paroxetine, fluoxetine, norfluoxetine and sertraline from clinical plasma and urine samples followed by ultra-HPLC-MS/MS assay. Results: The synthesized C18-Fe3O4@SiO2 NPs showed high magnetization and efficient extraction for the analytes. After cleanup by magnetic solid-phase extraction, no matrix effects were found in plasma and urine matrices. The analytes showed LODs among 0.15-0.75 ng ml-1, appropriate linearity (R ≥ 0.9990) from 2.5 to 1000 ng ml-1, acceptable accuracies 89.1-110.9% with precisions ≤11.0%. The protocol was successfully applied for the analysis of patients' plasma and urine samples. Conclusion: It shows high potential in routine therapeutic drug monitoring of clinical biological samples.


Assuntos
Antidepressivos/análise , Nanopartículas de Magnetita/química , Antidepressivos/isolamento & purificação , Antidepressivos/metabolismo , Cromatografia Líquida de Alta Pressão , Fluoxetina/análogos & derivados , Fluoxetina/sangue , Fluoxetina/isolamento & purificação , Fluoxetina/urina , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Paroxetina/sangue , Paroxetina/isolamento & purificação , Paroxetina/urina , Reprodutibilidade dos Testes , Sertralina/sangue , Sertralina/isolamento & purificação , Sertralina/urina , Dióxido de Silício/química , Extração em Fase Sólida , Solventes/química , Espectrometria de Massas em Tandem , Cloridrato de Venlafaxina/sangue , Cloridrato de Venlafaxina/isolamento & purificação , Cloridrato de Venlafaxina/urina
4.
Nutrients ; 11(12)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31756901

RESUMO

Geum japonicum, commonly known as Asian herb bennet, has been used as a diuretic, astringent, anti-dizziness, and anti-headache agent in traditional medicine. Since the antidepressant-like effects of G. japonicum extract have not been well studied, we examined the antidepressant-like effects of G. japonicum extract using depressive-like behavior induced in mice through daily injection of corticosterone (CORT). ICR mice (male, 8 weeks old) were treated with CORT (40 mg/kg, i.p.) and orally administered using oral gavage needles with G. japonicum extract (30, 100, and 300 mg/kg) for 4 weeks. Behavioral experiments were performed 1 h after administration. The control mice exhibited a significant increase in the immobility times in the tail suspension and forced swim tests as well as the step-through latency time in the passive avoidance test. Further, the control group showed a significant decrease in their sucrose consumption. However, treatment with G. japonicum extract at doses of 100 and 300 mg/kg significantly improved these depression-like behaviors without altering the locomotor activity. Moreover, treatment with G. japonicum extract significantly prevented the decrease in the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, G. japonicum extract had neuroprotective effects against CORT-induced neurotoxicity in SH-SY5Y cells. Our study indicates that G. japonicum extract exhibits antidepressant-like activity in CORT-induced depressive mice, which might be as a result of increased BDNF expression.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Corticosterona , Depressão/tratamento farmacológico , Geum , Extratos Vegetais/farmacologia , Animais , Antidepressivos/isolamento & purificação , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo , Linhagem Celular Tumoral , Depressão/induzido quimicamente , Depressão/fisiopatologia , Depressão/psicologia , Modelos Animais de Doenças , Comportamento Alimentar/efeitos dos fármacos , Geum/química , Humanos , Locomoção/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Tempo de Reação/efeitos dos fármacos , Fatores de Tempo
5.
Chem Biol Interact ; 314: 108843, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586550

RESUMO

Depression is a common neuropsychiatric disorder whose pathophysiology has been associated with glutamatergic excitotoxicity. Thus, the research for new antidepressant strategies with the ability to mitigate glutamate toxicity has received growing attention. Given this background, the present study sought to investigate the antidepressant-like and neuroprotective effects of Morus nigra (MN) and its major phenolic, syringic acid (SA), against glutamate-induced damage, as well as, the role of the PI3K/Akt/GSK-3ß signaling pathway in these effects. Treatment with MN (3 mg/kg) and SA (1 mg/kg) for 7 days, similar to fluoxetine (10 mg/kg), triggered an antidepressant-like effect. Moreover, the treatments evoked neuroprotection against glutamatergic excitotoxicity in hippocampal slices, and MN treatment also afforded protection in cerebrocortical slices. Notably, ex vivo neuroprotective effect of MN and SA was mediated, at least in part, by PI3K/Akt/GSK-3ß signaling pathway. Furthermore, the ability of MN and SA to counteract the glutamate-induced damage were evaluated in three different in vitro experiments. The hippocampal slices pretreated with MN (0.05 and 0.1 µg/mL) or SA (0.01-0.1 µg/mL) as well as the concomitant treatment with MN (0.01 and 0.05 µg/mL) or SA (0.05 and 0.1 µg/mL) exhibited protection against glutamate toxicity. Interestingly, post-treatment with MN in all doses (0.01-0.1 µg/mL) and SA at dose of 0.1 µg/mL were capable of preventing glutamate-induced cell death. In vitro neuroprotective effect of SA, but not MN, involves the activation of Akt, since the pretreatment with LY294002 completely abolished the protective effect. Overall, MN and SA presented antidepressant-like and neuroprotective effects against glutamatergic excitotoxicity via PI3K/Akt/GSK-3ß.


Assuntos
Antidepressivos/farmacologia , Ácido Gálico/análogos & derivados , Morus/química , Fármacos Neuroprotetores/farmacologia , Fenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antidepressivos/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Ácido Gálico/isolamento & purificação , Ácido Gálico/farmacologia , Ácido Glutâmico/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Morus/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Fenóis/isolamento & purificação , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/metabolismo
6.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470508

RESUMO

Viola betonicifolia (Violaceae) is commonly recognized as "Banafsha" and widely distributed throughout the globe. This plant is of great interest because of its traditional, pharmacological uses. This review mainly emphases on morphology, nutritional composition, and several therapeutic uses, along with pharmacological properties of different parts of this multipurpose plant. Different vegetative parts of this plant (roots, leaves, petioles, and flowers) contained a good profile of essential micro- and macronutrients and are rich source of fat, protein, carbohydrates, and vitamin C. The plant is well known for its pharmacological properties, e.g., antioxidant, antihelminthic, antidepressant, anti-inflammatory, analgesic, and has been reported in the treatment of various neurological diseases. This plant is of high economic value. The plant has potential role in cosmetic industry. This review suggests that V. betonicifolia is a promising source of pharmaceutical agents. This plant is also of significance as ornamental plant, however further studies needed to explore its phytoconstituents and their pharmacological potential. Furthermore, clinical studies are needed to use this plant for benefits of human beings.


Assuntos
Analgésicos/química , Anti-Helmínticos/química , Anti-Inflamatórios/química , Antidepressivos/química , Antioxidantes/química , Fármacos Neuroprotetores/química , Viola/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antidepressivos/isolamento & purificação , Antidepressivos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Humanos , Micronutrientes/classificação , Micronutrientes/isolamento & purificação , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Nutrientes/classificação , Nutrientes/isolamento & purificação , Fitoterapia/métodos , Componentes Aéreos da Planta/anatomia & histologia , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Extratos Vegetais/química , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/química , Plantas Medicinais , Viola/anatomia & histologia
7.
Neurochem Res ; 44(9): 2044-2056, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278631

RESUMO

Depression is a highly debilitating and life-threatening psychiatric disorder. The classical antidepressants are still not adequate due to undesirable side effects. Therefore, the development of new drugs for depression treatment is an urgent strategic to achieving clinical needs. Licorisoflavan A is a bioactive ingredient isolated from Glycyrrhizae Radix and has been recently reported for neuroprotective effects. In this study, the antidepressant-like effect and neural mechanism of licorisoflavan A were explored. In the mice behavioral despair test, we observed that licorisoflavan A exhibited powerful antidepressant-like effect in forced swimming test (FST), tail suspension test (TST), without affecting locomotor activity in open field test (OFT). Additionally, licorisoflavan A administration significantly restored Chronic mild stress (CMS)-induced changes in sucrose preference test (SPT), FST, and TST, without altering the locomotion in OFT. In chronical-stimulated mice, the licorisoflavan A treatment effectively attenuated the expressions of Brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), the phosphorylations of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK)-1/2, eukaryotic elongation factor 2 (eEF2), mammalian target of rapamycin (mTOR), initiation factor 4E-binding protein 1 (4E-BP-1), and p70 ribosomal protein S6 kinase (p70S6K) in hippocampus of CMS-induced mice. Additionally, licorisoflavan A could reverse the decreases in synaptic proteins post-synaptic density protein 95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) caused by CMS, and its antidepressant-like effect was blocked by the AMPA receptor antagonist NBQX. These findings served as preclinical evidence that licorisoflavan A exerted potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors. Licorisoflavan A might be used as a potential medicine against depression-like disorder.


Assuntos
Antidepressivos/uso terapêutico , Benzopiranos/uso terapêutico , Depressão/tratamento farmacológico , Receptores de AMPA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Antidepressivos/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Benzopiranos/isolamento & purificação , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hipocampo/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-31326644

RESUMO

Fabric phase sorptive extraction (FPSE), a recently introduced sorbent-based microextraction technique, was applied for the first time in order to achieve a simple and rapid simultaneous extraction of five common antidepressant drug residues (venlafaxine, paroxetine, fluoxetine, amitriptyline and clomipramine) from human blood serum. Elimination of protein precipitation step and minimized solvent consumption led to a sample preparation workflow compliant with the principles of green analytical chemistry (GAC). FPSE utilizes permeable and flexible fabric substrate chemically coated with a sol-gel organic-inorganic hybrid sorbent as the extraction device. Among all the membrane examined, sol-gel polycaprolactone-dimethylsiloxane-polycaprolactone coated polyester substrate presented optimum extraction efficiency and was found to be reusable for at least 30 times. The selected drugs were analyzed and detected by reversed phase high performance liquid chromatography method using gradient elution and a diode array detector operated at 235 nm. Limit of detection was found 0.15 ng µL-1, while good absolute recoveries (9.4-88.1%) and low relative standard deviations (≤9.2% and ≤ 11.0 for within-day and between-day precision, respectively) were obtained.


Assuntos
Antidepressivos/sangue , Antidepressivos/isolamento & purificação , Resíduos de Drogas/análise , Resíduos de Drogas/isolamento & purificação , Extração em Fase Sólida/métodos , Amitriptilina/sangue , Amitriptilina/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Humanos , Pirimidinas/sangue , Pirimidinas/isolamento & purificação , Extração em Fase Sólida/instrumentação
9.
Molecules ; 24(10)2019 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-31109124

RESUMO

Chiral metabolites of ketamine exerting rapid-onset yet sustained antidepressant effects may be marketed directly in the future, but require chemo- and enantio-selective chromatographic methods for quality assurance and control. The chromatographic behavior of S-/R-ketamine, S-/R-norketamine, S-/R-dehydronorketamine, and (2R,6R)-/(2S,6S)-hydroxynorketamine in supercritical fluid chromatography (SFC) was investigated computationally and experimentally with the aim of identifying problematic pairs of enantiomers and parameters for chiral resolution. Retention on three different polysaccharide-based chiral stationary phases (Lux Amylose-2, i-Amylose-3, and i-Cellulose-5) provided new information on the significance of halogen atoms as halogen bond donors and hydrogen bond acceptors for enantioselectivity, which could be corroborated in silico by molecular docking studies. Modifiers inversely affected enantioselectivity and retention. Methanol yielded lower run times but superior chiral resolution compared to 2-propanol. Lower temperatures than those conventionally screened did not impair phase homogeneity but improved enantioresolution, at no cost to reproducibility. Thus, sub-ambient temperature subcritical fluid chromatography (SubFC), essentially low-temperature HPLC with subcritical CO2, was applied. The optimization of the SubFC method facilitated the chiral separation of ketamine and its metabolites, which was applied in combination with direct injection and online supercritical fluid extraction to determine the purity of pharmaceutical ketamine formulations for proof of concept.


Assuntos
Antidepressivos/isolamento & purificação , Antidepressivos/metabolismo , Ketamina/isolamento & purificação , Ketamina/metabolismo , Amilose/química , Dióxido de Carbono/química , Celulose/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia com Fluido Supercrítico/métodos , Simulação de Acoplamento Molecular , Polissacarídeos/química , Reprodutibilidade dos Testes , Estereoisomerismo , Propriedades de Superfície , Temperatura
10.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1118-1119: 171-179, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054451

RESUMO

An innovative fabric phase sorptive extraction-high performance liquid chromatography-diode array detection (FPSE-HPLC-DAD) method is developed and validated herein for the simultaneous extraction and analysis of five common antidepressants (venlafaxine, paroxetine, fluoxetine, amitriptyline, clomipramine) in human urine samples. Separation was obtained using a reverse phase column LiChroCART-LiChrospher®100 RP-8e (5 µm, 250 × 4 mm) with diode array detection monitoring at 235 nm. Gradient elution was applied at a flow rate of 1.2 mL/min with a mobile phase that consisted of acetonitrile and ammonium acetate (0.05 M). Fabric Phase Sorptive Extraction was evaluated for the first time with regards to the extraction of the examined antidepressants from human urine and proved to be a rapid, simple, environmentally friendly, efficient, and selective sample preparation approach. Sol-gel graphene sorbent, coated on cellulose FPSE media, were the most efficient among other with different polarities. The absolute recovery values were 25.5% for venlafaxine, 33.9% for paroxetine, 67.0% for fluoxetine, 43.0% for amitriptyline and 29.0% for clomipramine, while relative recoveries were higher than 90%. The developed method provides satisfactory limit of detection 0.15 ng/µL.


Assuntos
Antidepressivos/isolamento & purificação , Antidepressivos/urina , Cromatografia Líquida de Alta Pressão/métodos , Antidepressivos/química , Desenho de Equipamento , Humanos , Limite de Detecção , Modelos Lineares , Modelos Moleculares , Reprodutibilidade dos Testes , Extração em Fase Sólida/instrumentação , Extração em Fase Sólida/métodos
11.
Neurochem Int ; 128: 206-214, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31077758

RESUMO

We have recently demonstrated that the hydroethanolic extracts of Impatiens glandulifera Royle (Balsaminaceae) have antianxiety effect in mice. The present study was aimed to investigate an antidepressant activity of hyperoside (HYP) and protocatechuic acid (PCA), two polyphenols isolated from the aerial parts of this plant, using the forced swimming test (FST) and tail suspension test (TST) in mice. The implication of the monoaminergic system in this effect was assessed and brain-derived neurotrophic factor (BDNF) expression was measured. At doses 1.875, 3.75 and 7.5 mg/kg, HYP and PCA significantly reduced immobility in the FST and TST, without affecting locomotor activity of mice. Pretreatment with p-chlorophenylalanine (PCPA 100 mg/kg, a serotonin synthesis inhibitor) or α-methyl-DL-tyrosine (AMPT 100 mg/kg, a catecholamine synthesis inhibitor) was able to prevent antidepressant-like effect of HYP and PCA (3.75 mg/kg). Sub-effective doses of fluoxetine (5 mg/kg) or reboxetine (2 mg/kg) were capable of potentiating the effect of a sub-effective dose of HYP (0.94 mg/kg) in the FST. Co-administration of sub-effective dose of PCA (0.94 mg/kg) and reboxetine (2 mg/kg) resulted in reducing immobility in the FST. The antidepressant-like effect of HYP and PCA was also prevented by the administration of sulpiride (50 mg/kg), a D2 antagonist. In addition, HYP (3.75 and 7.5 mg/kg) and PCA (7.5 mg/kg) improved the expression of hippocampal BDNF of mice subjected to TST. Altogether, our findings suggest that HYP and PCA exert antidepressant-like effects in mice, which was possibly mediated by monoaminergic system and the upregulation of BDNF level.


Assuntos
Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Depressão/metabolismo , Hidroxibenzoatos/uso terapêutico , Impatiens , Quercetina/análogos & derivados , Animais , Antidepressivos/isolamento & purificação , Antidepressivos/farmacologia , Aminas Biogênicas/biossíntese , Depressão/tratamento farmacológico , Depressão/psicologia , Relação Dose-Resposta a Droga , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia , Masculino , Camundongos , Componentes Aéreos da Planta , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Quercetina/isolamento & purificação , Quercetina/farmacologia , Quercetina/uso terapêutico , Natação/psicologia
12.
J Sep Sci ; 42(11): 2053-2061, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30945416

RESUMO

The growing use of antidepressants in recent years has led to their increasing presence in forensic analyses. In this work, microextraction by packed sorbent followed by ultra-performance liquid chromatography with photodiode array detection provided a fast method for determining the antidepressants mirtazapine, venlafaxine, escitalopram, fluoxetine, fluvoxamine, and sertraline in human urine. The microextraction conditions (viz., type of sorbent, number of draw-eject extraction cycles or strokes, sample volume and pH, and type and volume of washing solution and eluent) were optimized by using an experimental design. The ensuing analytical method was validated in terms of linearity (25-1000 ng/mL urine), limit of detection (lower than 7.1 ng/mL), limit of quantification (25 ng/mL), precision (4.7-15.1% as relative standard deviation), and accuracy (80.4-126.1% as mean recovery for four replicate determinations). The proposed method allowed the six target antidepressants to be determined at concentrations from therapeutic to toxic levels. The application to small volumes (300 µL) of urine afforded fast extraction of the analytes and provided results on a par with those of existing clinical and forensic alternatives.


Assuntos
Antidepressivos/isolamento & purificação , Antidepressivos/urina , Microextração em Fase Líquida/métodos , Cromatografia Líquida de Alta Pressão , Fluoxetina/análise , Fluoxetina/isolamento & purificação , Humanos , Limite de Detecção
13.
Artigo em Inglês | MEDLINE | ID: mdl-31017871

RESUMO

Background Adansonia digitata L. (Malvaceae) is used locally in the management of depressive illnesses, and its antidepressant-like effect has been previously reported. The present study was aimed at determining the effect of the methanol extract of the stem bark of A. digitata (MEAD) on chronic unpredictable mild stress (CUMS) and the possible mechanism responsible for its antidepressant activity. Methods Acute toxicity of MEAD was determined using the OECD guideline 420. The CUMS model was used to induce depression, and behavioral tests such as sucrose preference test (SPT), open field test (OFT), novel-object recognition test (NORT), and tail suspension test (TST) were carried out in mice. The concentrations of plasma cortisol and brain-derived neurotrophic factor (BDNF) protein in the brain were assessed using enzyme-linked immunosorbent assay kits. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed using colorimetric methods. Results The LD50 was established to be ≥5000 mg/kg. On CUMS-induced depression, MEAD significantly (p ≤ 0.05) and dose dependently reversed the weight loss, increased the line-crossing activity in OFT, increased sucrose consumption in SPT, decreased the duration of immobility in TST, and increased the novelty exploration time in NORT. The MEAD extract significantly (p ≤ 0.05) and dose dependently increased the levels of BDNF, decreased the levels of plasma cortisol, increased the levels of total SOD activity, and decreased the levels of plasma MDA. Conclusion Our findings show that MEAD ameliorates CUMS-induced depressive-like behavior and its effect is possibly mediated via the neuroendocrine, neurotrophic, and oxidative stress pathways.


Assuntos
Adansonia/química , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Antidepressivos/isolamento & purificação , Antidepressivos/toxicidade , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Doença Crônica , Depressão/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Sistema Hipotálamo-Hipofisário/metabolismo , Dose Letal Mediana , Metanol , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Casca de Planta/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Caules de Planta/química
14.
J Ethnopharmacol ; 236: 50-62, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30818006

RESUMO

AIMS: To explore the antidepressant- and anxiolytic-like effects of an aqueous extract of Turnera diffusa Willd (Turneraceae) and to explore its possible toxic side effects on behavior, target organ function, and spermatic quality. MATERIALS AND METHODS: Acute effects of a T. diffusa aqueous extract were evaluated in adult male mice with the plus-maze, forced swimming and open field tests to identify the possible anxiolytic, antidepressant and stimulant effects of this extract. Effects of T. diffusa aqueous extract were further investigated through two approaches. a) Male and female adult mice receiving a 28-day treatment were evaluated in a neurobehavioral test battery; later, changes in their biochemical parameters and in target organ morphology were analyzed. b) In young adult (16-weeks old) and mature (46-weeks old) males, spermatic quality and testes morphology during a complete spermatogenesis cycle were analyzed after a 35-day treatment. RESULTS: T. diffusa aqueous extract induced remarkable anxiolytic- and antidepressant-like effects without affecting locomotor activity. This extract did not elicit behavioral signs of neural side effects, a sex-dependent reduction in body weight gain was produced without affecting functional parameters or the morphology of target organs. The highest dose improved cellular turnover in the testes of mature mice. CONCLUSION: T. diffusa aqueous extract induced a clear anxiolytic-like effect, and for the first time, we reported an antidepressant effect. Clinical potential or even intake of T. diffusa in the context of traditional medicine can be supported by its efficacy to positively modulate behavior and its safety for a wide range of doses.


Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Turnera/química , Animais , Ansiolíticos/isolamento & purificação , Ansiolíticos/toxicidade , Antidepressivos/isolamento & purificação , Antidepressivos/toxicidade , Relação Dose-Resposta a Droga , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Especificidade de Órgãos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Teste de Desempenho do Rota-Rod , Espermatogênese/efeitos dos fármacos , Natação , Testículo/efeitos dos fármacos , Testículo/patologia
15.
J Sep Sci ; 42(8): 1620-1628, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30758140

RESUMO

In the present study, a supramolecular solvent was formed from reverse micelle aggregates of octanol. The proposed supramolecular solvent was used for rapid extraction of some antidepressants drugs including amitriptyline, imipramine, desipramine, maprotiline, sertraline, and doxepin from biological samples. Alkanol-based supramolecular solvents have a unique array of physicochemical properties, making them a very attractive alternative to replace organic solvents in analytical extractions. The parameters affecting the extraction of target analytes (i.e., the volume of tetrahydrofuran and octanol as the major components comprising the supramolecular solvent, chain length of alkanols, sample solution pH, salt addition, and ultrasonic time) were investigated and optimized by factor by factor optimization method. Under the optimum conditions, preconcentration factors of 470, 490, 460, 385, 370, and 430 were obtained for amitriptyline, doxepin, imipramine, desipramine, maprotiline, and sertraline, respectively. The linear ranges and coefficients of determination (R2 ) were obtained in the range of 0.01-100 µg/L and 0.9974-0.9991, respectively. Also the limits of detection (S/N = 3) of 0.003-0.03 µg/L, and precisions (n = 5) of 4.9-8.9% were calculated. Finally, the method was successfully applied for the extraction of antidepressant drugs in biological samples, and relative recoveries in the range of 91-102% were obtained.


Assuntos
Antidepressivos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Líquida/métodos , Ultrassom/métodos , Antidepressivos/sangue , Antidepressivos/urina , Furanos/química , Humanos , Limite de Detecção , Octanóis/química , Solventes/química
16.
Pak J Pharm Sci ; 32(1): 81-87, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772794

RESUMO

The study is conducted to observe and investigate the effects of oral dosing of methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) on neuropharmacological activities of mice. Methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) were soluble in Dimethyl sulphoxide (DMSO) i.e. an organic solvent, so it is used in this study. Screening for anxiolytic and antidepressant effects were performed using open field test, head dip test, stationary rod test, cage crossing test, light and dark box and swimming- induced depression test. Thirty animals were divided into three groups of 10 animals each and numbered as 1 (control, on DMSO), 2(on methanolic extract of Cuminum nigrum (L), 3 (on methanolic extract of Centratherum anthelminticum (L). The extracts and DMSO were administered orally for 60 days. Any possible change in animal behavior was evaluated on day 15, 30 and 60 of dosing. The groups 2 and 3 showed significant increase (p<0.001, p<0.01) in open field activity and light and dark box test respectively, while significantly decreased activity was observed in head dip and cage crossing activity (p<0.01) after 60 days of dosing. Based on above findings, it is suggested that the extracts of Centratherum anthelminticum (L) and Cuminum nigrum (L) have antidepressant and anxiolytic potential with sedative effects.


Assuntos
Asteraceae , Comportamento Animal/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/farmacologia , Cuminum , Metanol/química , Extratos Vegetais/farmacologia , Solventes/química , Animais , Ansiolíticos/isolamento & purificação , Ansiolíticos/farmacologia , Antidepressivos/isolamento & purificação , Antidepressivos/farmacologia , Asteraceae/química , Fármacos do Sistema Nervoso Central/isolamento & purificação , Cuminum/química , Comportamento Exploratório/efeitos dos fármacos , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Aprendizagem/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Sementes
17.
Phytochemistry ; 161: 28-40, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30802641

RESUMO

Incensole and its acetate have shown anti-inflammatory and anti-depression activities due to their ability to activate ion channels in the brain to alleviate anxiety or depression. The natural occurrence of these two structurally and medicinally fascinating 14-membered diterpenoids was reported mainly from the genus Boswellia. Incensole and incensole acetate were detected in and isolated from both essential oils and resins of frankincense. One total synthesis was reported for incensole. Both incensole and its acetate served as precursors for several synthetic transformations. Given the fact that no specific enzymes were isolated from Boswellia trees, the major sources for incensole and incensole acetate, the biosynthetic pathway of these two compounds was only speculated. Recent studies on incensole and incensole acetate including ours have revealed another secret of the ancient drug. Understanding their mode of action will open a door in modern neurobiology and provides new insights on the mysterious diseases of the nervous system. This review interpretatively discusses the natural existence of incensole and incensole acetate, the variation of their percentages in different Boswellia species and other sources, their synthetic modifications, their biosynthesis and their therapeutic potential.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antidepressivos/uso terapêutico , Boswellia/química , Transtorno Depressivo/tratamento farmacológico , Diterpenos/uso terapêutico , Inflamação/tratamento farmacológico , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antidepressivos/química , Antidepressivos/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos
18.
Fitoterapia ; 133: 180-185, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30659875

RESUMO

Aquilariaenes A-H (1-8), eight new diterpenoids and nor-diterpenoids (1-8) belonging to abietane or pimarane, were isolated from the petroleum ether extract of Chinese eaglewood. Their structures were elucidated on the basis of extensive spectroscopic methods including HRESIMS, IR, 1D and 2D NMR spectroscopic data analyses. Antidepressant activities of isolates for in vitro inhibition of serotonin and norepinephrine reuptake in rat brain synaptosomes were evaluated.


Assuntos
Antidepressivos/farmacologia , Diterpenos/farmacologia , Sinaptossomos/efeitos dos fármacos , Thymelaeaceae/química , Animais , Antidepressivos/isolamento & purificação , Diterpenos/isolamento & purificação , Estrutura Molecular , Norepinefrina/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Ratos , Serotonina/metabolismo
19.
J Cell Physiol ; 234(6): 8496-8508, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30461013

RESUMO

BACKGROUND: Psychiatric disorders are substantially associated with reduced quality of life and increased mortality. Depression and anxiety are two of the most common psychiatric disorders that often co-occur with each other as well as with other mental health conditions. Because of the limitations of currently available antidepressant therapies, there is a need for agents with improved efficacy and less adverse effects. Hypericum perforatum, widely known as St. John's wort, is a perennial herbaceous plant most well known for its antidepressant properties. METHODS: We reviewed the available in vitro, in vivo, and clinical evidence on the efficacy, safety, and mechanisms of action of St. John's wort and its active constituents in the treatment of psychiatric and neurodegenerative disorders. RESULTS: Several interesting data have been reported about the antidepressant properties of H. perforatum in clinical trials with different designs. In particular, a number of antidepressant-controlled trials demonstrated that H. perforatum and its active ingredients, hypericin and hyperforin, possess antidepressant properties similar to those of tricyclic antidepressants and selective serotonin reuptake inhibitors but with fewer and milder side effects. CONCLUSION: St. John's wort may exert potent antidepressant effects and represents an efficacious and safe treatment. However, the current clinical evidence regarding the efficacy of H. perforatum in other psychiatric and neurodegenerative disorders is not sufficient to draw a robust conclusion.


Assuntos
Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Antiparkinsonianos/uso terapêutico , Hypericum , Nootrópicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Ansiolíticos/efeitos adversos , Ansiolíticos/isolamento & purificação , Antidepressivos/efeitos adversos , Antidepressivos/isolamento & purificação , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/isolamento & purificação , Humanos , Hypericum/efeitos adversos , Hypericum/química , Nootrópicos/efeitos adversos , Nootrópicos/isolamento & purificação , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação
20.
J Pharm Pharmacol ; 71(1): 117-128, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28653745

RESUMO

BACKGROUND: Extracts of Hypericum perforatum, more commonly known as St John's wort (SJW), have good evidence for treating depression. The herb is easily accessible and widely used by consumers, although it has potential for interaction with other medicines. Consumers' use of SJW is often not discussed with their general practitioners (GPs). It is unclear how GPs perceive use of SJW in practice and the implications for consumers and pharmacists. OBJECTIVE: Explore GPs' perception of SJW use in practice. METHODS: Scoping review. KEY FINDINGS: Few studies explore GPs' perceptions of SJW for depression, but they appear to recommend it infrequently, except in Germany. Reasons for limited use in practice include lack of knowledge, particularly regarding which preparations and dosages have trial evidence, and lack of standardisation of active ingredients. Guidelines either do not mention SJW or advise against its use. CONCLUSIONS: Consumers drive SJW use but often do not disclose to their GPs, which is concerning due to issues about safety. Pharmacists could play an important role here. Improved education about SJW is required for both GPs and consumers, including the need for communication between them and their pharmacists. Lack of adoption of evidence-based therapy for depression should be explored further.


Assuntos
Depressão/tratamento farmacológico , Hypericum/química , Extratos Vegetais/uso terapêutico , Antidepressivos/efeitos adversos , Antidepressivos/isolamento & purificação , Antidepressivos/uso terapêutico , Atitude do Pessoal de Saúde , Revelação , Clínicos Gerais/psicologia , Clínicos Gerais/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Farmacêuticos/organização & administração , Extratos Vegetais/efeitos adversos , Papel Profissional
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