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1.
Planta Med ; 86(1): 26-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31711251

RESUMO

Kava, the extract of the roots of Piper methysticum, has been traditionally consumed in the South Pacific islands for its natural relaxing property. Epidemiological data suggests that kava consumption may reduce human cancer risk, and in vitro and in vivo models suggest chemopreventive potential against carcinogen-induced tumorigenesis. Therefore, knowledge about its molecular mechanisms and responsible ingredient(s) for these beneficial properties will better guide kava's use for the management of these disorders. Psychological stress typically results in increased production of stress hormones, such as norepinephrine (NE), which activate adrenergic receptors (ARs). Psychological stress has also been associated with increased cancer incidence and poor clinical outcomes in cancer patients. Mechanistically, binding of NE to ARs induces intracellular calcium influx, which activates downstream signaling pathways involved in both stress and cancer development. In this study, we characterized the effect of kava and its components, 3 fractions and 6 major kavalactones, on NE-induced intracellular calcium influx in H1299, a human non-small cell lung carcinoma cell line. Results show that kava extract effectively inhibits NE-mediated intracellular calcium influx in H1299 cells, potentially through antagonizing ß-AR signaling. This inhibitory activity is recapitulated by the major kavalactones in kava. Among the 6 major kavalactones, DHK demonstrated the best potency. Taken together, our study suggests a novel mechanism through which kava and its ingredients potentially offer the anxiolytic and cancer-preventive activity.


Assuntos
Ansiolíticos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Cálcio/metabolismo , Kava/química , Lactonas/farmacologia , Neoplasias Pulmonares/prevenção & controle , Extratos Vegetais/farmacologia , Ansiolíticos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Lactonas/isolamento & purificação , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/psicologia , Norepinefrina/antagonistas & inibidores , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico
2.
Life Sci ; 239: 116869, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678277

RESUMO

AIM: The addition of repeated lipopolysaccharide (LPS) to chronic mild stress was recently proposed in our lab as an alternative model of depression, highlighting the possible interaction between stress and immune-inflammatory pathways in predisposing depression. Given that CMS-induced depressive behavior was previously related to impaired hippocampal energy metabolism and mitochondrial dysfunction, our current study aimed to investigate the interplay between toll-like receptor 4 (TLR4) signaling and peroxisome proliferator-activated receptor gamma coactivators-1-alpha (PGC1-α) as a physiological regulator of energy metabolism and mitochondrial biogenesis in the combined LPS/CMS model. MAIN METHODS: Male Wistar rats were exposed to either LPS (50 µg/kg i.p.) over 2 weeks, CMS protocol for 4 weeks or LPS over 2 weeks followed by 4 weeks of CMS (LPS/CMS). Three additional groups of rats were exposed to LPS/CMS protocol and treated with either pentoxifylline (PTX), fluoxetine (FLX) or a combination of both. Rats were examined for behavioral, neurochemical, gene expression and mitochondrial ultra-structural changes. KEY FINDINGS: LPS/CMS increased the expression of TLR4 and its downstream players; MyD88, NFκB and TNF-α along with an escalation in hippocampal-energy metabolism and p-AMPK. Simultaneously LPS/CMS attenuated the expression of PGC1-α/NRF1/Tfam and mt-DNA. The antidepressant (AD) 'FLX', the TNF-α inhibitor 'PTX' and their combination ameliorated the LPS/CMS-induced changes. Interestingly, all the aforementioned changes induced by the LPS/CMS combined model were significantly less than those induced by CMS alone. SIGNIFICANCE: Blocking the TLR4/NFκB signaling enhanced the activation of the PGC1-α/NRF1/Tfam and mt-DNA content independent on the activation of the energy-sensing kinase AMPK.


Assuntos
Fluoxetina/farmacologia , Mitocôndrias/efeitos dos fármacos , Pentoxifilina/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , DNA Mitocondrial/metabolismo , Metabolismo Energético , Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Biogênese de Organelas , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/induzido quimicamente , Fator de Necrose Tumoral alfa/metabolismo
3.
Biomed Res Int ; 2019: 5705232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612144

RESUMO

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.


Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Panax/química , Serotonina/metabolismo , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Depressão/genética , Depressão/fisiopatologia , Transtorno Depressivo/genética , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Elevação dos Membros Posteriores/métodos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Ratos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Natação
4.
Artigo em Chinês | MEDLINE | ID: mdl-31623042

RESUMO

Objective:The aim of this study is to investigate the effects of rhodiola rosea on oxidative stress, anxiety and depression in patients with OSA. Method:Ninety patients with moderate and severe OSA patients with negative emotions diagnosed by PSG, self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were selected from the respiratory department of our hospital from February 2015 to February 2018. According to the random number table method, the patients were randomly divided into non-invasive ventilator group, rhodiola rosea+non-invasive ventilator group and rhodiola rosea group, with 30 cases in each group. Patients in the non-invasive ventilator group were treated with continuous positive airway pressure (CPAP) for 3 months, and those in the rhodiola rosea+non-invasive ventilator group were treated with oral rhodiola capsules for 3 months on the basis of CPAP, and those in the rhodiola rosea treatment group were treated with pure oral rhodiola capsules for 3 months. The changes of SDS and SAS before and after the three groups were compared, and the changes of serum SOD and MDA were detected by immunoenzyme-linked adsorption for comparative analysis. Result:There were no significant differences in SDS and SAS scores between the three groups (P>0.05). SDS and SAS scores of patients in the rhodiola rosea+non-invasive ventilator group decreased after treatment (P<0.05) compared with those in the non-invasive ventilator group. SDS and SAS scores of patients in the rhodiola treatment group increased after treatment (P<0.05). Compared with those in the rhodiola treatment group, SDS and SAS scores of patients in the rhodiola+non-invasive breathing group decreased after treatment (P<0.05). Three group patients were no significant difference in serum SOD and malondialdehyde (MDA) before treatment (P>0.05). Compared with before treatment, serum SOD level were all increased and MDA level were all decreased in the three groups after treatment (P<0.05). Compared with noninvasive breathing unit after treatment, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased (P<0.05), and for the treatment group after treatment in patients with serum SOD levels drop, the MDA levels (P<0.05), and the after rhodiola rosea treatment group compared, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased (P<0.05). Conclusion:Rhodiola may improve the negative emotions such as anxiety and depression by inhibiting oxygen free radicals and lipid peroxidation in patients with OSA.


Assuntos
Extratos Vegetais/uso terapêutico , Rhodiola , Apneia Obstrutiva do Sono/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Malondialdeído , Estresse Oxidativo/efeitos dos fármacos
5.
Medicine (Baltimore) ; 98(37): e17186, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517876

RESUMO

BACKGROUND: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. METHODS: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. RESULTS: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). CONCLUSIONS: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).


Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Adulto , Ansiolíticos/efeitos adversos , Ansiedade/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/efeitos adversos , Estresse Psicológico/metabolismo , Testosterona/metabolismo , Resultado do Tratamento
6.
Molecules ; 24(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540539

RESUMO

Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.


Assuntos
Depressão , Dipterocarpaceae/química , Etanol/química , Extratos Vegetais , Folhas de Planta/química , Estresse Psicológico , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/patologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Proteínas Imediatamente Precoces/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos ICR , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas Serina-Treonina Quinases/biossíntese , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia
7.
Orthopade ; 48(11): 957-962, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31559467

RESUMO

BACKGROUND: Rheumatic and mental disorders are common and affect each other. The comorbidities are often diagnosed too late or not at all but cause considerable suffering for those affected and have a negative effect on the health-related quality of life and therapeutic success. OBJECTIVES: Is there any evidence regarding common pathophysiological mechanisms and how can they be considered in terms of therapy? METHODS: Recent findings, reviews and basic literature are analyzed and an update is presented and discussed. RESULTS: The current data suggest a mutual influence of the factors stress and inflammation both in depressive disorders, anxiety disorders and chronic pain, as well as in diseases of the rheumatic type. There is a close relationship between immunological and neuronal processes that bi-directionally regulate the individual's stress response. CONCLUSIONS: For sufficient therapy the establishment of an interdisciplinary treatment concept in clinical everyday life is to be striven for. In addition to rheumatic treatment, this should include a multimodal approach to both pharmacological and psycho-socio-therapeutic components. In particular, potential interactions must be taken into account.


Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Inflamação , Doenças Reumáticas/psicologia , Estresse Psicológico/epidemiologia , Antidepressivos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Comorbidade , Depressão , Humanos , Inflamação/epidemiologia , Inflamação/psicologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Qualidade de Vida , Doenças Reumáticas/epidemiologia , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/psicologia
8.
Nutrients ; 11(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527485

RESUMO

A systematic review and meta-analysis was undertaken to examine and quantify the effects of B vitamin supplementation on mood in both healthy and 'at-risk' populations. A systematic search identified all available randomised controlled trials (RCTs) of daily supplementation with ≥3 B group vitamins with an intervention period of at least four weeks. Random effects models for a standardized mean difference were used to test for overall effect. Heterogeneity was tested using the I2 statistic. Eighteen articles (16 trials, 2015 participants) were included, of which 12 were eligible for meta-analysis. Eleven of the 18 articles reported a positive effect for B vitamins over a placebo for overall mood or a facet of mood. Of the eight studies in 'at-risk' cohorts, five found a significant benefit to mood. Regarding individual facets of mood, B vitamin supplementation benefited stress (n = 958, SMD = 0.23, 95% CI = 0.02, 0.45, p = 0.03). A benefit to depressive symptoms did not reach significance (n = 568, SMD = 0.15, 95% CI = -0.01, 0.32, p = 0.07), and there was no effect on anxiety (n = 562, SMD = 0.03, 95% CI = -0.13, 0.20, p = 0.71). The review provides evidence for the benefit of B vitamin supplementation in healthy and at-risk populations for stress, but not for depressive symptoms or anxiety. B vitamin supplementation may particularly benefit populations who are at risk due to (1) poor nutrient status or (2) poor mood status.


Assuntos
Afeto/efeitos dos fármacos , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Suplementos Nutricionais , Estresse Psicológico/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Deficiência de Vitaminas do Complexo B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Resultado do Tratamento , Complexo Vitamínico B/efeitos adversos , Deficiência de Vitaminas do Complexo B/diagnóstico , Deficiência de Vitaminas do Complexo B/epidemiologia , Deficiência de Vitaminas do Complexo B/psicologia , Adulto Jovem
9.
Biomed Pharmacother ; 118: 109263, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31369988

RESUMO

It is well known that chamomile is one of the oldest known medicinal herbs and has been used to treat various disorders, but it is mainly German chamomile. The effects of Roman chamomile on depression still unclear. In this study, we used chronically stressed mice to investigate whether inhalation of Roman chamomile essential oil affects depression-like behavior. We previously reported that restraint and water immersion stress produce depression-like behavior and a blunted response to the tricyclic antidepressant clomipramine. Each mouse was exposed to restraint and water immersion stress for 15 days, and resistance to the effect of clomipramine was induced in a behavioral despair paradigm. In the present study, we found that cotreatment with clomipramine and inhalation of Roman chamomile attenuated depression-like behavior in a forced swim test. Next, we examined the hippocampal mRNA levels of two cytokines, tumor necrosis factor (TNF) alpha and interleukin-6 (IL-6); a neurotrophic factor, brain derived-neurotrophic factor (BDNF); and nerve growth factor (NGF). TNF alpha, IL-6 and BDNF mRNA levels did not change in the hippocampus of stressed mice. However, the NGF mRNA level was significantly decreased, and this decrease was not attenuated by treatment with clomipramine or inhalation of Roman chamomile alone. We also examined whether Roman chamomile combined with clomipramine treatment affects hippocampal neurogenesis and serum corticosterone levels. Stressed mice had fewer doublecortin (DCX)-positive cells in the subgranular zone of the dentate gyrus, but this was significantly attenuated by Roman chamomile and clomipramine treatment. In addition, the serum corticosterone level was also significantly decreased by treatment with Roman chamomile and clomipramine. These results suggest that Roman chamomile inhalation may enhance the antidepressant effect of clomipramine by increasing hippocampal neurogenesis and modulating corticosterone levels in patients with treatment-resistant depression.


Assuntos
Comportamento Animal , Chamaemelum/química , Clomipramina/uso terapêutico , Depressão/tratamento farmacológico , Exposição por Inalação , Extratos Vegetais/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Clomipramina/farmacologia , Corticosterona/sangue , Citocinas/genética , Citocinas/metabolismo , Depressão/sangue , Quimioterapia Combinada , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Neurogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estresse Psicológico/sangue , Estresse Psicológico/tratamento farmacológico
11.
Pharmacol Biochem Behav ; 185: 172763, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31445955

RESUMO

Pharmacotherapy and cognitive behavioral therapy, both fail to treat post-traumatic stress disorder (PTSD) in a considerable number of populations. The persistence of traumatic memories and deficit in extinction contributes to the failure of exposure therapy in PTSD. With the objective to enhance the outcomes of exposure therapy by targeting the extinction window using pharmacological agents in PTSD, the present study was aimed to explore the effect of piracetam, risperidone and their combinations in experimentally-induced PTSD-like phenotype in rats. Male SD rats were exposed to single prolonged stress model (SPS) for induction of PTSD-like behavioral changes. Piracetam, risperidone and their combination were used as therapeutic interventions while sertraline was used as a standard treatment for 14 days along with extinction training. Induction of PTSD-like behaviors were assessed in behavioral tests such as fear conditioning, elevated plus maze, social interaction test, and the marble burying test. Neurotransmitters (dopamine and serotonin and their metabolites), BDNF, proinflammatory cytokines (TNF-α, IL-6), caspase-3, and markers for oxidative stress were assessed in the hippocampus and cortex while corticosterone and nitrite levels were estimated in plasma. Our result indicated that the SPS paradigm efficiently induced PTSD-like phenotype in rats. Risperidone and piracetam were found to be effective alone, while their high dose combination, produced potentiating effect in reversing the extinction deficit, behavioral alterations, altered cortical and hippocampal BDNF, IL-6, TNF-α, caspase-3, oxidative stress markers, and neurotransmitter levels. Plasma corticosterone and nitrite levels were also found to be reversed in the combination treated groups. Our preliminary study suggests that piracetam, risperidone and their combination restored the physiological cascades in cortex and hippocampus along with successful suppression of fear memory and a symptom cluster of PTSD-like phenotype in rats. Hence they could be used as an effective adjunct to enhance the outcome of exposure therapy for the management of PTSD.


Assuntos
Antipsicóticos/farmacologia , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Piracetam/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Risperidona/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Antipsicóticos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Corticosterona/sangue , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Piracetam/administração & dosagem , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-Dawley , Risperidona/administração & dosagem , Estresse Psicológico/tratamento farmacológico
12.
Biol Pharm Bull ; 42(8): 1268-1274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366864

RESUMO

Increasing evidence shows depression relevant to oxidative stress and inflammation. Anti-inflammatory strategies or antioxidants have led to the development of new antidepressants. Brazilin is a natural product from the Chinese traditional medicine Caesalpinia sappan L., exerting anti-inflammatory, antioxidant, anti-platelet concentration, and anti-cancer effects. While the antidepressant effect of brazilin is largely unknown. In present study, we investigated the effects of brazilin on H2O2-induced oxidative injury in PC12 cells and on depression- and anxiety-like behaviors of chronically mild stressed (CMS)-induced depression mice. It was found that brazilin pre-treatment (both 10 and 20 µM) significantly increased cell viability and decreased cell apoptosis in H2O2-treated PC12 cells. Furthermore, repetitive administration of brazilin to CMS-induced depression mice by intraperitoneal injection (10 mg/kg) made the mice significantly lose their latency of feeding in novelty-suppressed feeding test (NSF), have more the sucrose preference in sucrose preference test (SPT), and more time spent in the central zone without affecting their crossing activity in open field test (OFT). These results suggested that brazilin can play a role in antidepressant and anxiolytic-like behaviors for CMS-induced depression mice probably through inhibiting the oxidative stress. Therefore, brazilin is worth to be further explored for treating depressive and anxiety disorders.


Assuntos
Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Benzopiranos/uso terapêutico , Depressão/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzopiranos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos
13.
Biol Pharm Bull ; 42(8): 1402-1408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366875

RESUMO

Beta-cryptoxanthin (ß-CRX, (3R)-ß, ß-caroten-3-ol) is an oxygenated carotenoid and a potent antioxidant that is abundant in Satsuma mandarin orange (Citrus unshiu MARC.), which is the most popular fruit in Japan. Since our preliminary data suggested that the ingestion of ß-CRX had an anti-stress effect in female participants, the effect was evaluated in another set of female participants. The study design was a double-blind group comparison and participants (n = 23) were randomly assigned to ß-CRX-rich orange juice or placebo (ß-CRX was removed from orange juice) groups. ß-CRX or placebo juice (125 mL, after breakfast) were consumed from 1 week prior to pharmacy practice and continued for 5 d into the practice period. Salivary α-amylase activity (sAA), a marker of sympathetic nervous system activity, was significantly higher in the evening than in the morning in the placebo-group during pharmacy practice, but not in the ß-CRX-group. This result supports the anti-stress effect of ß-CRX. The dose-dependency of ß-CRX was observed in male mice that were loaded with stress. These results indicate that the ingestion of ß-CRX is helpful to reduce stress.


Assuntos
beta-Criptoxantina/farmacologia , Citrus , Sucos de Frutas e Vegetais , alfa-Amilases Salivares/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Glândulas Suprarrenais/efeitos dos fármacos , Adulto , Animais , Método Duplo-Cego , Feminino , Frutas , Humanos , Masculino , Camundongos , Estresse Psicológico/metabolismo , Adulto Jovem
14.
Int Immunopharmacol ; 75: 105799, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401387

RESUMO

Depression is a chronic, severe, and often life-threatening disease accompanied with impaired neurogenesis. Evidence showed that neuroinflammation played a key role in the process of depression. High mobility group protein box 1 (HMGB1) has been proved to function as a pro-inflammatory cytokine. In this study, we used a social defeat (SD) stress to induce inflammatory response, aiming to explore the relationship between HMGB1 and neuroinflammation. We found that the expression of HMGB1 decreased in mice exposure to SD stress, but showed a high expression of cytoplasmic HMGB1 and a high expression of RAGE, which could be rescued by ICA and ICT. So, we speculated that the translocation of HMGB1 from the nucleus to the cytoplasm might play an important role in neuroinflammatory process, and HMGB1-RAGE signaling was involved in this process. Furthermore, we also found that TLR4-XBP1s-ER stress related NF-κB signaling activation was also involved in HMGB1-related neuroinflammation. However, ICA and ICT treatment activated NF-κB signaling, and we also observed the translocation of HMGB1 into the nucleus and the increased number of neurons in mice hippocampus, indicating that the activation of NF-κB signaling might be related to neuroregeneration. Moreover, recombinant human HMGB1 protein (rHMGB1) pretreatment could suppress HMGB1-RAGE signaling and TLR4-XBP1s-ER stress related NF-κB signaling, resulted in a suppressed microglia activation in mice hippocampus. We supposed that ICA and ICT could ameliorate neuroinflammation in hippocampus via suppressing HMGB1-RAGE signaling and show neuroprotective effects via activating TLR4- NF-κB signaling at the same time, resulting in improving depressive behaviors in mice.


Assuntos
Anti-Inflamatórios/uso terapêutico , Flavonoides/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Citocinas/sangue , Citocinas/genética , Modelos Animais de Doenças , Flavonoides/farmacologia , Proteína HMGB1/sangue , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/metabolismo
15.
Food Funct ; 10(9): 5886-5897, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31464319

RESUMO

Gut microbiota dysbiosis is a recognized contributing factor to many noncommunicable diseases, but more evidence is still needed to illustrate its causative impact on mental and brain health disorders and mechanism(s) for targeted mitigation. Traditional Chinese Medicine (TCM) has been used in the management of neuropsychiatric diseases for many years in China. In this study, a randomized, controlled trial was conducted to examine the impact of stress on gut microbiota dysbiosis and depression, and TCM in alleviating the damage using Chronic Unpredictable Mild Stress (CUMS) rats, a well-established rodent model for depression. The behaviors of rats and the profiles of the fecal microbiota were assessed by an array of behavioral tests and 16S rRNA gene sequencing, and the intestinal microbial function was assessed by shotgun sequencing-based metagenomic analysis of microbial DNA from fecal samples. Data on brain targeted metabolites by liquid chromatography-mass spectrometry (LC-MS) were also discussed. Depressive and anxiety-like behaviors and changes in the fecal microbiota profile were observed in CUMS rats, which were then significantly reversed in CUMS rats that received TCM. Specifically, TCM treatment reduced the levels of Firmicutes, and Ruminococcus, and increased the abundance of Bacteroidetes and Roseburia, reportedly being associated with relieving psychiatric disorders. Furthermore, the levels of brain metabolites perturbed by CUMS were reversed by TCM treatment, and Spearman's correlation analysis illustrated strong correlation between brain metabolites and perturbed fecal microbiota genera. Finally, the fecal microbiome of CUMS rats was characterized by alterations in amino acid metabolism and evaluation of bile acid biosynthesis, and TCM-treated rats showed elevation of cysteine and methionine metabolism. Overall, these results indicated that administration of the TCM may mitigate CUMS-induced depression-behaviors, and it is correlated with reversing CUMS-induced intestinal microbiota dysbiosis; evidence also supported related changes in brain metabolites. These findings set up the foundation to further reveal the exact causal relationship among the TCM formula, host responses, gut microbiota dysbiosis and the levels of brain metabolites, and enabled scientific interpretation of the therapeutic function of the TCM.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Plantas Medicinais/química , Estresse Psicológico/tratamento farmacológico , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Depressão/microbiologia , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Disbiose/psicologia , Fezes/microbiologia , Humanos , Masculino , Medicina Tradicional Chinesa , Ratos , Estresse Psicológico/microbiologia , Estresse Psicológico/psicologia
16.
Biomed Res Int ; 2019: 1926352, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428628

RESUMO

The mortality of individuals suffering from depression has been increasing, noticeably of postmenopausal women; consequently, their care and treatment are significant to retain a high quality of life. The aim of this study was to examine the effect of Camellia sinensis (CS) on repeated stress-induced changes of the depression related function on the tail suspension test (TST), forced swimming test (FST) in ovariectomized female rats. After behavioral test, we evaluated the changes in the neurotransmitter by measuring the level of dopamine in the nucleus accumbens (NaC) and the serum levels of estrogen and oxytocin. We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of CS on glucose metabolism in ovariectomized rats. Female rats were randomly segregated into three groups. Nor group was considered as nonoperated and nonstressed group, while the control was the ovariectomized and stressed group (OVX+ST), and CS was the ovariectomized, stressed and CS treated group. The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and CS (300 mg/kg, i.p.) was treated 30 min before IMO stress. Significant reduction of immobility in the TST and FST was indicated in rats treatment with CS compared to the control group (OVX+ST). The levels of estrogen in the serum of the Nor and CS groups were significantly elevated compared to the OVX+ST group. Also, CS activated brain glucose metabolism in the cortex. The present findings suggested that CS had antidepressant effectiveness in a menopausal depression animal model. These findings suggest evidence that CS plays a crucial role in stressful situation, providing that CS might be a dependable antidepressant medicine to treat menopausal depression.


Assuntos
Camellia sinensis/química , Córtex Cerebral , Glucose/metabolismo , Extratos Vegetais/farmacologia , Tomografia por Emissão de Pósitrons , Estresse Psicológico , Animais , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Menopausa/metabolismo , Ovariectomia , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo
17.
Phytother Res ; 33(12): 3177-3190, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31468620

RESUMO

The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant-like effects. We observed that SD aggravated the anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant-like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3ß/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant-like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK and PI3K/AKT/GSK3ß/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.


Assuntos
Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Schisandra/química , Privação do Sono/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doença Crônica , Modelos Animais de Doenças , Humanos , Masculino , Camundongos
18.
Biol Pharm Bull ; 42(7): 1146-1154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257291

RESUMO

Helicid (4-formylphenyl-O-ß-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Benzaldeídos/farmacologia , Benzaldeídos/uso terapêutico , Depressão/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Cognição/efeitos dos fármacos , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Depressão/metabolismo , Depressão/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiologia , Aprendizagem/efeitos dos fármacos , Masculino , Neurogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-31318691

RESUMO

Background The 5HT4 receptor agonists are antidepressants with a unique mode of action. Many studies have been done on investigational drugs, and mosapride has been shown to have a 5HT3 antagonistic property. In this study, we assessed the potential anxiolytic and antidepressant effects of mosapride on Wistar albino rats. Methods The rats were randomly assigned to two models containing 4 groups of 6 animals each. In the anxiety model, four groups included 0.5 mL of 0.5% carboxymethyl cellulose (CMC), mosapride 1.5 mg/kg, mosapride 3 mg/kg and diazepam 2 mg/kg. They were dosed for 5 days. On the 3rd day, the elevated plus maze (EPM) was conducted, and on the 5th day, the open field (OF) tests were conducted. In the depression model, four groups included 0.5 mL of 0.5% CMC, mosapride 1.5 mg/kg, mosapride 3 mg/kg and imipramine 30 mg/kg. After 3 days of dosing, the forced swim test (FST) was conducted, followed by a washout period of 1 month. Then, the rats were subjected to chronic unpredictable stress with sucrose preference. Results Compared with the control, the mosapride-treated animals showed significant anxiolytic behavior at both high and low doses in the EPM and OF tests. In the FST, both high and low doses of mosapride reduced immobility. The climbing behavior was prominent at a high dose of mosapride, whereas swimming was prominent at a low dose. In the chronic stress model, both doses of mosapride preserved sucrose preference comparable to imipramine. Conclusion These findings suggest that mosapride has anxiolytic and antidepressant activities at clinically used doses.


Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Ansiedade/tratamento farmacológico , Benzamidas/farmacologia , Depressão/tratamento farmacológico , Morfolinas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar , Estresse Psicológico/tratamento farmacológico , Natação/fisiologia
20.
J Ethnopharmacol ; 243: 112079, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31302206

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-Zi-Hou-Po decoction (ZZHPD), a classical Chinese prescription, has been reported to improve depressive behaviors in clinic. However, definite pharmacological effects and mechanisms of ZZHPD on monoaminergic system and hippocampal neurogenesis are ambiguous. It need to be further illuminated. AIM OF THE STUDY: Our study is designed to reveal pharmacological mechanisms of ZZHPD on depression through pharmacokinetics, monoamine neurotransmitters and neurogenesis. MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS) is used to establish rats model of depression. Then, the antidepressant effects of ZZHPD are evaluated by detecting body weight, sucrose preference and forced swimming test. The regulatory functions of ZZHPD on monoaminergic system are assessed by measuring monoamine neurotransmitters, neurotransmitter precursor substances, synthesized rate-limiting enzymes and transporters. Finally, potential molecular mechanism of ZZHPD on hippocampal neurogenesis is evaluated by investigating newborn immature neuron and newborn mature neuron. RESULTS: Our results show that ZZHPD remarkably normalizes CUMS-induced decline in weight gain, decrease of sucrose consumption rate in sucrose preference test and increase of immobility time in forced swimming test. Moreover, ZZHPD significantly reverses CUMS-induced reduction of 5-hydroxytryptamine (5-HT), dopamine (DA), tryptophan (Trp), tyrosine (Tyr), tryptophan hydroxylase2 (TPH2) and tyrosine hydroxylase (TH), whereas decreases level of serotonin transporter (SERT) in CUMS-induced rats. Finally, ZZHPD obviously improves CUMS-induced decrease of newborn immature neuron and newborn mature neuron in dentate gyrus of hippocampus. CONCLUSION: This study demonstrates that ZZHPD can alleviate CUMS-induced depression-like behaviors. It is probably attributed to the fact that ZZHPD could enhance monoaminergic system and hippocampal neurogenesis. Our findings provide the new perspectives on molecular targets of ZZHPD, and it will facilitate its clinical application.


Assuntos
Antidepressivos/farmacologia , Depressão/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Iridoides/farmacologia , Estresse Psicológico/metabolismo , Animais , Antidepressivos/uso terapêutico , Monoaminas Biogênicas/metabolismo , Doença Crônica , Depressão/tratamento farmacológico , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Iridoides/farmacocinética , Iridoides/uso terapêutico , Masculino , Neurogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Estresse Psicológico/tratamento farmacológico , Triptofano Hidroxilase/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
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