RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin, a bioactive compound extracted from the traditional Chinese herb, Paeonia lactiflora Pall, has been demonstrated to possess efficient antidepressant activity in previous studies. AIM OF THE STUDY: Our systematic review and meta-analysis aimed to assess the effectiveness of paeoniflorin in relieving depressive-like behaviors in animal models. MATERIALS AND METHODS: We searched for in vivo studies on the antidepressant effects of paeoniflorin in rodents using electronic databases from their inception to April 2021. The measurements of animal behavioral tests, including the sucrose consumption, forced swimming, tail suspension, and open field tests, were regarded as the outcomes. RESULTS: Fourteen studies involving 416 animals met the inclusion criteria and were included in the meta-analysis. Statistical analysis revealed remarkable differences between the paeoniflorin and control groups. Furthermore, the paeoniflorin group showed great efficiency in improving depressive-like symptoms of animals in the sucrose consumption, forced swimming, tail suspension, and open field tests. CONCLUSIONS: Our meta-analysis demonstrates that paeoniflorin can significantly improve depressive-like symptoms in animals and suggests that it can be a potential therapy for patients with depression in the future.
Assuntos
Antidepressivos/farmacologia , Depressão/patologia , Medicamentos de Ervas Chinesas/farmacologia , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Paeonia , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Camundongos , RatosRESUMO
Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. A novel treatment that can directly influence the neural circuit relevant to an individual patient's subset of symptoms might more precisely and thus effectively aid in the alleviation of their specific symptoms. We tested this hypothesis in a proof-of-concept study using fMRI functional connectivity neurofeedback. We targeted connectivity between the left dorsolateral prefrontal cortex/middle frontal gyrus and the left precuneus/posterior cingulate cortex, because this connection has been well-established as relating to a specific subset of depressive symptoms. Specifically, this connectivity has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. Furthermore, a posterior cingulate dominant state-which results in a loss of this anticorrelation-is expected to specifically relate to an increase in rumination symptoms such as brooding. In line with predictions, we found that, with neurofeedback training, the more a participant normalized this connectivity (restored the anticorrelation), the more related (depressive and brooding symptoms), but not unrelated (trait anxiety), symptoms were reduced. Because these results look promising, this paradigm next needs to be examined with a greater sample size and with better controls. Nonetheless, here we provide preliminary evidence for a correlation between the normalization of a neural network and a reduction in related symptoms. Showing their reproducibility, these results were found in two experiments that took place several years apart by different experimenters. Indicative of its potential clinical utility, effects of this treatment remained one-two months later.Clinical trial registration: Both experiments reported here were registered clinical trials (UMIN000015249, jRCTs052180169).
Assuntos
Transtornos de Ansiedade/prevenção & controle , Conectoma/métodos , Depressão/prevenção & controle , Córtex Pré-Frontal Dorsolateral/fisiologia , Rede Nervosa/fisiologia , Neurorretroalimentação/métodos , Adulto , Transtornos de Ansiedade/patologia , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico , Estudos de Casos e Controles , Depressão/patologia , Depressão/psicologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Medical personnel working in emergency rooms (ER) are at increased risk of mental health problems and suicidality. There is increasing evidence that mindfulness-based interventions can improve burnout and other mental health outcomes in health care providers. In contrast, few longitudinal prospective studies have examined protective functions of dispositional mindfulness in this population. The objective of this study was to examine whether mindfulness prospectively predicts anxiety, depression, and social impairment in a sample of emergency care professionals. The authors administered online surveys to ER personnel prior to work in ER, and at 3 and 6 months follow up. Participants were 190 ER personnel (73% residents, 16% medical students, 11% nurses). Linear mixed effects regression was used to model longitudinal 3-month and 6-month follow up of depression, anxiety, and social impairment. Predictors included time-varying contemporaneous work stressors, perceived social support at work and life events, and baseline dispositional mindfulness, demographics, and workplace characteristics. Mindfulness indexed when starting ER work predicted less depression, anxiety, and social impairment 6 months later. Mindfulness remained a strong predictor of mental health outcomes after controlling for time-varying stressful events in emergency care, negative life events, and social support at work. Mindfulness moderated the adverse impact of poor social support at work on depression. To our knowledge, this is the first longitudinal study to show that mindfulness prospectively and robustly predicts anxiety, depression, and social impairment. Results support the role of mindfulness as a potential resilience factor in at-risk health care providers.
Assuntos
Ansiedade/patologia , Depressão/patologia , Pessoal de Saúde/psicologia , Atenção Plena/métodos , Adulto , Serviços Médicos de Emergência , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Estresse Ocupacional , Apoio Social , Inquéritos e Questionários , Local de TrabalhoRESUMO
Given the growing evidence that a range of lifestyle factors are involved in the etiology of depression, a 'lifestyle medicine' approach can be potentially safe and cost-effective to prevent or treat depression. To examine the effects and acceptability of a group-based, integrative lifestyle medicine intervention as a standalone treatment for managing depressive symptoms, a pilot randomized controlled trial (RCT) was conducted in a Chinese adult population in 2018. Participants (n = 31) with PHQ-9 score above the cut-off of ≥ 10, which was indicative of moderate to severe depression, were recruited from the general community in Hong Kong and randomly assigned to lifestyle medicine group (LM group) or care-as-usual group (CAU group) in a ratio of 1:1. Participants in the LM group received 2-hour group sessions once per week for six consecutive weeks, which covered diet, exercise, mindfulness, psychoeducation, and sleep management. Linear mixed-effects model analyses showed that the LM group had a significant reduction in PHQ-9 scores compared to the CAU group at immediate posttreatment and 12-week posttreatment follow-up (d = 0.69 and 0.73, respectively). Moreover, there were significantly greater improvements in anxiety, stress, and insomnia symptoms (measured by DASS-21 and ISI) at all time points in the LM group (d = 0.42-1.16). The results suggests that our 6-week group-based, integrative lifestyle intervention program is effective in lowering depressive, anxiety, stress, and insomnia symptoms in the Chinese population. Further studies in clinical populations with a larger sample size and longer follow-up are warranted.
Assuntos
Ansiedade/terapia , Depressão/terapia , Atenção Plena , Distúrbios do Início e da Manutenção do Sono/terapia , Adulto , Ansiedade/epidemiologia , Ansiedade/patologia , Ansiedade/prevenção & controle , Análise Custo-Benefício , Depressão/epidemiologia , Depressão/patologia , Depressão/psicologia , Terapia por Exercício , Feminino , Hong Kong/epidemiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono/patologia , Distúrbios do Início e da Manutenção do Sono/prevenção & controleRESUMO
Catalpol is a major compound in Rehmanniae Radix with outstanding medicinal and nutritional values. Our previous studies have demonstrated catalpol's antidepressant effect, but its mechanisms remain unclear. This study aimed to explore the antidepressant mechanisms of catalpol via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1 (HO-1) pathway. Results demonstrated that chronic unpredictable mild stress (CUMS) for 5 consecutive weeks caused significant decreases in the sucrose preference and the horizontal and vertical scores of open-field test, as well as a significant increase in the swimming-immobility time of rats; catalpol administration significantly reversed the abnormality of these indicators. Further real-time fluorescent quantitative polymerase chain reaction and Western blotting results together showed that CUMS significantly downregulated the expression levels of hippocampal genes and proteins, including PI3K, Akt, Nrf2, HO-1, tropomyosin-related kinase B (TrkB), and brain-derived neurotrophic factor; catalpol administration significantly reversed the abnormal expression of these genes and proteins. CUMS also caused a significant decrease in the hippocampal superoxide dismutase, catalase, glutathione peroxidase, glutathione-s transferase, and reduced glutathione levels, as well as a significant increase in thiobarbituric acid reactive substances level in rats; catalpol administration significantly reversed the abnormality of these indicators. Taken together, this study confirmed for the first time that the antidepressant effect of catalpol on CUMS-induced depression involved the upregulation of the PI3K/Akt/Nrf2/HO-1 signaling pathway, thereby improving the hippocampal neurotrophic, neuroprotective, and antioxidant levels. The PI3K/Akt/Nrf2/HO-1 pathway-related molecules may serve as potential new biomarkers and candidate molecular targets for catalpol's antidepressant effects.
Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Hipocampo/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Animais , Antidepressivos/uso terapêutico , Depressão/diagnóstico , Depressão/etiologia , Depressão/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Heme Oxigenase (Desciclizante)/metabolismo , Hipocampo/patologia , Humanos , Glucosídeos Iridoides/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/complicaçõesRESUMO
Depressive state adversely affects the memory functions, especially in the geriatric population. The initial stage of memory deficits associated with depression is particularly called as pseudodementia. It is the starting point of memory disturbance before dementia. The purpose of this research was to study depression and its consequent pseudodementia. For this purpose 24 male albino Wistar rats were divided into four groups. Depression was induced by 14 days of chronic restraint stress (CRS) daily for 4 h. After developing a depression model, pattern separation test was conducted to monitor pseudodementia in rats. Morris water maze test (MWM) was also performed to observe spatial memory. It was observed that model animals displayed impaired pattern separation and spatial memory. Treatment was started after the development of pseudodementia in rats. Curcumin at a dose of 200 mg/kg was given to model rats for one week along with the stress procedure. Following the treatment with curcumin, rats were again subjected to the aforementioned behavioral tests before decapitation. Corticosterone levels, brain derived neurotrophic factor (BDNF) and neurochemical analysis were conducted. Model rats showed depressogenic behavior and impaired memory performance. In addition to this, high corticosterone levels and decreased hippocampal BDNF, 5-HT, dopamine (DA), and acetylcholine (ACh) levels were also observed in depressed animals. These behavioral biochemical and neurochemical changes were effectively restored following treatment with curcumin. Hence, it is suggested from this study that pseudodementia can be reversed unlike true dementia by controlling the factors such as depression which induce memory impairment.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Curcumina/farmacologia , Depressão/tratamento farmacológico , Dopamina/metabolismo , Transtornos Autoinduzidos/prevenção & controle , Hipocampo/efeitos dos fármacos , Neurotransmissores/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Corticosterona/metabolismo , Depressão/metabolismo , Depressão/patologia , Transtornos Autoinduzidos/etiologia , Transtornos Autoinduzidos/metabolismo , Transtornos Autoinduzidos/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ratos , Ratos Wistar , Estresse FisiológicoRESUMO
BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear. PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms. METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored. RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling. CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Depressão/patologia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Antidepressivos/farmacologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Comorbidade , Depressão/tratamento farmacológico , Depressão/epidemiologia , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1-/- mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves's tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies.
Assuntos
Canais Iônicos Sensíveis a Ácido/genética , Dor Crônica/genética , Depressão/genética , Canais de Cátion TRPV/genética , Ácidos/toxicidade , Pontos de Acupuntura , Animais , Cerebelo/metabolismo , Cerebelo/patologia , Cerebelo/efeitos da radiação , Dor Crônica/induzido quimicamente , Dor Crônica/complicações , Dor Crônica/terapia , Comorbidade , Depressão/complicações , Depressão/patologia , Modelos Animais de Doenças , Eletroacupuntura , Humanos , Camundongos , Camundongos Knockout , Solução Salina/toxicidade , NataçãoRESUMO
Protective effects of Puerariae flos extract (PFE) on ethanol (EtOH) exposure have been previously verified. This study attempts to explore the protective effects of PEF on EtOH withdrawal models. Sixty male Kunming mice were involved which were randomly divided into five groups (intact control, EtOH group (35-day EtOH exposure), EtOH withdrawal group (28-day exposure + 7-day withdrawal), EtOH withdrawal group + positive control (Deanxit) group, and EtOH withdrawal group + PFE group). The changes of neuropsychological behaviors; hippocampal BDNF expression and CA1 neuronal density; and plasma corticotropin-releasing hormone (CRH), ACTH, and CORT levels were observed. It was found that depression-like behaviors reduced by EtOH exposure and increased by withdrawal under the 28-day EtOH exposure and 7-day withdrawal conditions. In addition, anxiety-like behaviors worsened by EtOH exposure and unchanged by withdrawal. Deanxit and PEF ameliorated such behaviors (vs. withdrawal group). Hippocampal BDNF expression was significantly downregulated by EtOH exposure and upregulated by withdrawal. Deanxit and PEF significantly upregulated the BDNF expression. The hippocampal CA1 neuronal density significantly decreased by EtOH exposure but unchanged by withdrawal and treatments. The plasma CRH, ACTH, and CORT levels show a significant enhancement by EtOH exposure and reduced by withdrawal. They were further reduced by Deanxit and PEF. The protective effects of PEF on EtOH chronic withdrawal mouse models were verified. The results of this study also indicated a complicated scenario of neuropsychological behaviors, hippocampal BDNF expression, and hypothalamic-pituitary-adrenal axis which are affected by the timing of EtOH exposure and withdrawal.
Assuntos
Alcoolismo/tratamento farmacológico , Ansiedade/prevenção & controle , Região CA1 Hipocampal/efeitos dos fármacos , Depressão/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Pueraria , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Hormônio Adrenocorticotrópico/sangue , Alcoolismo/metabolismo , Alcoolismo/patologia , Alcoolismo/psicologia , Animais , Ansiedade/metabolismo , Ansiedade/patologia , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Hormônio Liberador da Corticotropina/sangue , Depressão/metabolismo , Depressão/patologia , Depressão/psicologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Masculino , Camundongos , Pueraria/química , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/patologia , Síndrome de Abstinência a Substâncias/psicologiaRESUMO
Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammation in this subtype of depression. We also discuss downstream mechanisms mediating the link between inflammation and symptoms of depression, including alterations in dopaminergic neurotransmission and tryptophan metabolism. Finally, we review evidence for several non-pharmacological interventions for inflammatory depression, including probiotics, omega-3 fatty acids, and physical exercise interventions. While some evidence suggests that these interventions may be efficacious in inflammatory depression, future clinical trials should consider enriching patient populations for inflammatory markers, or stratify patients by inflammatory status, to confirm or refute this hypothesis.
Assuntos
Depressão/patologia , Transtorno Depressivo Maior/patologia , Terapia por Exercício/métodos , Ácidos Graxos Ômega-3/uso terapêutico , Microbioma Gastrointestinal/fisiologia , Probióticos/uso terapêutico , Proteína C-Reativa/análise , Proteína C-Reativa/líquido cefalorraquidiano , Depressão/imunologia , Depressão/terapia , Transtorno Depressivo Maior/terapia , Neurônios Dopaminérgicos/fisiologia , Disbiose/microbiologia , Exercício Físico/fisiologia , Humanos , Inflamação/patologia , Inflamação/psicologia , Transmissão Sináptica/fisiologia , Triptofano/metabolismoRESUMO
Origanum majorana L. is a plant commonly used in folk medicine to treat depression and several neurological disorders. This study aims to evaluate the antidepressant-like effect of the Origanum majorana L. polyphenols (OMP) obtained from the aerial parts using two different depression model tests: The forced swimming test (FST) and the tail suspension test (TST) in Swiss albino mice. The experiments were performed on days 1, 7, 14, and 21 with daily administration of different treatments. Two different doses were chosen for this study (50 and 100 mg/kg), and paroxetine was used as a positive control. Immobility as a consequence of the depression state was significantly reduced following the treatment with OMP, indicating an antidepressant effect. A subacute toxicity study was also performed following the Organization for Economic Co-operation and Development (OECD) Guidelines (407), showing no sign of toxicity for the studied doses. The phytochemical screening revealed the presence of 12 components, all belonging to polyphenols: Arbutin, rosmarinic acid, ursolic acid, quercetin-3-O-glucoside, quercetin-7-O-glucuronic acid, luteolin-7-O-glucoside, kaempferol-3-0-glucuronic acid, Kaempferol-3-0-pentose, caffeic acid, catechin, quercetin, and rutin. These findings suggest that O. majorana has interesting antidepressant-like properties, which deserve further investigation.
Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Origanum/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Animais , Antidepressivos/toxicidade , Depressão/patologia , Elevação dos Membros Posteriores , Masculino , Camundongos , Extratos Vegetais/toxicidade , Polifenóis/toxicidade , Natação , Testes de ToxicidadeRESUMO
The prefrontal lobe has been considered to be closely related to depression. This study examined the relationship between depression and three prefronto-thalamic tract (PF-TT) regions (the dorsolateral prefronto-thalamic tract [DLPF-TT], ventrolateral prefronto-thalamic tract [VLPF-TT], and the orbitofronto-thalamic tract [OF-TT]) in patients with mild traumatic brain injury (TBI), using diffusion tensor tractography (DTT). Thirty-seven patients with depression following mild TBI were recruited based on Beck Depression Inventory-II (BDI-II) scores. Thirty-one normal control subjects were also recruited. The three regions of the PF-TTs were reconstructed using probabilistic tractography and DTT parameters for each of the three PF-TT regions were determined. The tract volume of the DLPF-TT and OF-TT in the patient group showed a significant decrease compared to that of the control group (p < 0.05). The BDI-II score of the patient group showed a moderate negative correlation with the tract volume value of the right (r = - 0.33) and left (r = - 0.41) DLPF-TT (p < 0.05). On the other hand, no significant correlations were detected between the BDI-II score of the patient group and the values of the other DTT parameters values for the three PF-TT regions (p > 0.05). Using DTT, depression was found to be closely related to a DLPF-TT injury in patients with mild TBI. We believe that evaluation of the DLPF-TT using DTT would be helpful when assessing patients with depression following mild TBI. These results can provide useful information regarding the proper application of neuromodulation in the management of depression.
Assuntos
Concussão Encefálica/complicações , Depressão/patologia , Córtex Pré-Frontal/patologia , Tálamo/patologia , Substância Branca/patologia , Adolescente , Adulto , Idoso , Depressão/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/lesões , Prognóstico , Tálamo/lesões , Substância Branca/lesões , Adulto JovemRESUMO
Accumulating evidence has demonstrated that oxidative stress is associated with depression. Our present study aimed at investigating the antidepressant effect and the possible mechanisms of curcumin (CUR) in chronic unpredictable mild stress- (CUMS-) induced depression model in rats. After exposure to CUMS for four weeks, the rats showed depressive-like behavior, and the depressive-like behaviors in CUMS-treated rats were successfully corrected after administration of CUR. In addition, CUR could effectively decrease protein expression of oxidative stress markers (Nox2, 4-HNE, and MDA) and increase the activity of CAT. CUR treatment also reversed CUMS-induced inhibition of Nrf2-ARE signaling pathway, along with increasing the mRNA expression of NQO-1 and HO-1. Furthermore, the supplementation of CUR also increased the ratio of pCREB/CREB and synaptic-related protein (BDNF, PSD-95, and synaptophysin). In addition, CUR could effectively reverse CUMS-induced reduction of spine density and total dendritic length. In conclusion, the study revealed that CUR relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway.
Assuntos
Comportamento Animal/efeitos dos fármacos , Curcumina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/sangue , Curcumina/uso terapêutico , Depressão/tratamento farmacológico , Depressão/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Banxia Houpu decoction (BXHPD) has been used to treat depression in clinical practice for centuries. However, the pharmacological mechanisms of BXHPD still remain unclear. Network Pharmacology (NP) approach was used to explore the potential molecular mechanisms of BXHPD in treating depression. Potential active compounds of BXHPD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database. STRING database was used to build a interaction network between the active compounds and target genes associated with depression. The topological features of nodes were visualized and calculated. Significant pathways and biological functions were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 44 active compounds were obtained from BXHPD, and 121 potential target genes were considered to be therapeutically relevant. Pathway analysis indicated that MAPK signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway and PI3K-Akt pathway were significant pathways in depression. They were mainly involved in promoting nerve growth and nutrition and alleviating neuroinflammatory conditions. The result provided some potential ways for modern medicine in the treatment of depression.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Bases de Dados Factuais , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/patologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Ontologia Genética , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa , Redes e Vias Metabólicas/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacosRESUMO
Depression is the most significant risk factor for suicide, yet the causes are complex and disease mechanism remains unclear. The incidence and disability rate of depression are very high and the efficacy of some traditional antidepressants is not completely satisfactory. Recently, some studies have found that benzofurans have anti-oxidation and anti-monoamine oxidase properties, which are related to depression. Euparin is a monomer compound of benzofuran, previous work by our team found that it improves the behavior of depressed mice. However, additional antidepressant effects and mechanisms of Euparin have not been reported. In this study, the Chronic Unpredictable Mild Stress (CUMS) model of mice was used to further investigate the effect and mechanism of Euparin on depression. Results showed that Euparin (8, 16 and 32 mg/kg) reduced depression-like behavior in mice compared with the model group. Meanwhile, all doses of Euparin were found to increase the contents of monoamine neurotransmitter and decrease monoamine oxidase and reactive oxygen species (ROS) levels in brain of depression mice. Additionally, Euparin restored CUMS-induced decrease of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1), N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) and brain derived neurotrophic factor (BDNF) expression. These findings demonstrate that Euparin has antidepressant properties, and its mechanism involves the SAT1/NMDAR2B/BDNF signaling pathway.
Assuntos
Benzofuranos/farmacologia , Depressão/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/complicações , Acetiltransferases/metabolismo , Animais , Técnicas de Observação do Comportamento , Comportamento Animal/efeitos dos fármacos , Benzofuranos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/diagnóstico , Depressão/patologia , Depressão/psicologia , Modelos Animais de Doenças , Dopamina , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Camundongos , Neurotransmissores/metabolismo , Norepinefrina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Serotonina/metabolismo , Organismos Livres de Patógenos Específicos , Estresse Psicológico/psicologiaRESUMO
Piper laetispicum C. DC is one of the Chinese herbal medicines used for alleviating depressive disorders. G11-5 [3-(3, 4-methylenedioxy-5-trifluoromethyl phenyl)-2E-propenoic acid isobutyl amide] is synthesized based on the chemical structure of an active integrant of Piper laetispicum C. DC. The present study assessed the antidepressant effect of G11-5 and investigated the underlying mechanism with learned helplessness (LH) and social defeat stress (SDS) mice model of depression. In the LH model, mice were exposed to 60 inescapable electric shocks once a day for three consecutive days followed by 2-week drug administration and helpless behaviour assessment. In the SDS model, mice were subjected to repeated social defeat by an aggressive CD-1 mouse once a day for consecutive 10 days. Following oral administration for 2 weeks, the mice were subjected to a series of behavioural tests including social interaction test. G11-5 significantly decreased the number of escape failures induced by LH paradigm, meanwhile increased the social interaction ratio and shortened the immobility time in forced swimming test for the SDS-exposed mice, suggesting remarkable antidepressant effect. Moreover, G11-5 ameliorated the changes in mitophagy-related proteins induced by two stress exposures and restored retrograde axonal transport and neurotransmitter release. Our findings suggested that G11-5 exhibited an obvious antidepressant through TSPO-mediated mitophagy pathway.
Assuntos
Amidas/farmacologia , Antidepressivos/farmacologia , Benzodioxóis/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Receptores de GABA/metabolismo , Estresse Psicológico/tratamento farmacológico , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/patologia , Depressão/psicologia , Teste de Labirinto em Cruz Elevado , Desamparo Aprendido , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Mitofagia/efeitos dos fármacos , Piper/química , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Derrota Social , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Estresse Psicológico/psicologia , NataçãoRESUMO
The treatment of depressive symptoms of bipolar disorder (BD) has received increasing attention. Recently, some studies have shown that bright light therapy (BLT) seems to be useful for BD depression. This meta-analysis is intended to further elucidate the role of BLT in depressive symptoms in patients with BD. Register of Systematic Reviews PROSPERO: CRD 420191 33642.Randomized controlled trials and cohort studies were retrieved in PubMed, Cochrane Library, EMbase, Web of Science, CINHAL, CBM, CNKI, VIP, and Wanfang from their foundation to March 2020, and other sources as supplement was also retrieved. Data were extracted after strict evaluation of literature quality by two researchers, and Meta-analysis was conducted on literatures that met the inclusion criteria. Meta-analysis was performed using Revman 5.3 software. In total, 12 studies including 847 patients with BD depression were included in our meta-analysis. A meta-analysis found significant differences between BLT and placebo for the following outcomes: (1) depression severity before and after BLT [SMD = -0.43, 95% CI (-0.73,-0.13), P<0.05] in RCT and [SMD = -2.12, 95% CI (-2.3,-1.94), P<0.05] in cohort studies.; (2) the efficacy of duration/timing of light therapy for depressive symptoms in BD [I2 = 85%, SMD = -1.88, 95% CI (-2.04, -1.71),P<0.05] and [I2 = 71%, SMD = -2.1,95% CI(-2.24, -1.96), P<0.05]; (3) the efficacy of different color/color temperatures for depressive symptoms in BD [I2 = 0%, SMD = -0.56, 95% CI (-0.92, -0.19), P<0.05] and [I2 = 97%, SMD = -1.74, 95% CI (-1.99, -1.49), P<0.05].We performed a subgroup meta-analysis of studies that used different light intensities. The results showed that light intensity≥5000 lux significantly reduced the severity of depression. And patients without psychotropic drugs revealed significantly decreased disease severity [I2 = 0%, SMD = -0.6, 95% CI (-1.06,-0.13), P<0.05]. Limitations of the study include studies only assessed short-term effects, and insufficient duration may underestimate adverse reactions and efficacy. Our results highlight the significant efficiency of BLT in the treatment of bipolar depression. Prospective studies with more rigorous design and consistent follow-up.
Assuntos
Transtorno Bipolar/terapia , Depressão/terapia , Fototerapia , Transtorno Bipolar/complicações , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/patologia , Depressão/complicações , Depressão/epidemiologia , Depressão/patologia , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Depression is the most common form of mental illness and the major cause of disability worldwide. Symptoms of depression, including feelings of intense sadness and hopelessness, may occur after a specific event or in response to a gradual decline in health and functional status, often associated with aging. Current therapies for treating these symptoms include antidepressant drugs, counseling and behavioral therapy. However, antidepressant drugs are associated with mild to severe adverse effects, which has prompted the need for better treatment options. Medicinal mushrooms are valuable sources of food and medicine and are increasingly being used as supplements or as alternative medicines in standard healthcare. Numerous studies have provided insights into the neuroprotective effects of medicinal mushrooms, which are attributed to their antioxidant, anti-neuroinflammatory, cholinesterase inhibitory and neuroprotective properties. In this review, we comprehensively examine the role of these medicinal mushrooms in the treatment of depression. However, to apply these natural products in clinical settings, the therapeutic agent needs to be properly evaluated, including the active ingredients, the presence of synergistic effects, efficient extraction methods, and stabilization of the active ingredients for delivery into the body as well as crossing the blood-brain barrier.
Assuntos
Agaricales/química , Agaricales/metabolismo , Agaricus/química , Agaricus/metabolismo , Animais , Antidepressivos/química , Antidepressivos/isolamento & purificação , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/patologia , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Medicina Tradicional , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêuticoRESUMO
AIMS AND OBJECTIVES: To classify hemodialysis patients into subgroups via cluster analysis according to the Somatic Symptoms Disturbance Index, Taiwanese Depression Scale, and Herth Hope Index scores. Patient demands in each cluster were also examined. BACKGROUND: Overall patient demands among hemodialysis patients have been demonstrated in numerous reports; however, variables among subgroups have not been explored. METHODS: Data were analyzed from a cross-sectional survey of 114 hemodialysis patients recruited from dialysis centers in Northern Taiwan. Hope, depression, and symptom disturbance were used as parameters for clustering because they have been shown to be important factors affecting patient demands. A two-step cluster analysis was performed to classify participants into clusters. Patient demands in each cluster were analyzed. RESULTS: Among the 114 participants, there was a negative correlation between hope and depression as well as between hope and symptom disturbance; there was a positive correlation between depression and symptom disturbance. Two clusters were identified: Cluster 1 (n = 49) included patients with moderate levels of hope and symptom disturbance, and high levels of depression; and Cluster 2 (n = 65) included patients with low levels of depression and symptom disturbance and high levels of hope. Demographic profiles differed between the two clusters. Regarding patient demands, medical demand showed the highest average score; whereas, occupational demand exhibited the lowest average score. Psychological and occupational demands differed significantly between the two clusters. The two clusters were defined as subgroups: Cluster 1 was labeled "resting"; Cluster 2 was labeled "active". CONCLUSIONS: Cluster analysis may further classify hemodialysis patients into distinct subgroups base on their specific patient demands. A better understanding of patient demands may help health professionals to provide a holistic individualized treatment to improve patients' outcomes.
Assuntos
Falência Renal Crônica/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Estudos Transversais , Depressão/patologia , Feminino , Esperança , Humanos , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Taiwan , Adulto JovemRESUMO
BACKGROUND: Menopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain. METHODS: Therefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX. RESULTS: Our data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions. CONCLUSION: Collectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.