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ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. AIM OF THE STUDY: To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. RESULTS: There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. CONCLUSIONS: These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.
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Antidepresivos , Depresión , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Animales , Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Ratones , Masculino , Línea Celular , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Corticosterona/sangre , Espectrometría de Masas en Tándem , Conducta Animal/efectos de los fármacosRESUMEN
BACKGROUND: Hemifacial spasm (HFS) is a debilitating disease characterized by involuntary tonic and clonic contractions of muscles innervated by the facial nerve. Botulinum toxin A (BTX-A) is the first-line option and the most effective medical treatment for HFS. The objective of this study was to evaluate the effect of BTX-A therapy on the physical and mental health of HFS patients. METHODS: Participants included 65 HFS patients and 65 matched healthy controls in the study. Cornell Medical Index (CMI) self-assessment questionnaire was used to detect the psychological health of all participants. Local injection of BTX-A was applied, and the Cohen hierarchical criteria were employed to stratify the degree of spasticity, further evaluating the efficacy of BTX-A before and two months after treatment in HFS patients. The HFS patients at two months post-treatment were re-evaluated by CMI self-assessment questionnaire, and the evaluated factors of these patients were compared with those of patients before treatment. RESULTS: The scores of somatization, depression, anxiety, inadaptation, sensitivity, anger, tension, M-R, and total scores in the HFS group were significantly higher than those in the control group (all P<0.05). Two months post-treatment, among 65 HFS patients who received with BTX-A treatment, 42 (64.6%) were completely relieved, 16 (24.6%) were significantly relieved, 7 (10.8%) were partially relieved, and 0 (0%) cases were invalid, and the total effective rate was 89.2%. Two months after BTX-A treatment, the scores of somatization, tension, anxiety, depression, sensitivity, M-R and total scores of patients with HFS were lower than those before treatment (all P<0.05). CONCLUSIONS: Patients with HFS are often accompanied by somatization, anger, inadaptation, sensitivity, anxiety, depression, and tension. BTX-A can not only alleviate the symptoms of HFS, but also improve the somatization, tension, anxiety, depression, and sensitivity.
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Toxinas Botulínicas Tipo A , Espasmo Hemifacial , Fármacos Neuromusculares , Humanos , Espasmo Hemifacial/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares/uso terapéutico , Adulto , Salud Mental , Resultado del Tratamiento , Anciano , Encuestas y Cuestionarios , Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológicoRESUMEN
BACKGROUND: Effective medication adherence is vital for managing acute myocardial infarction (AMI) and enhancing patient well-being. This study aimed to evaluate medication adherence levels and associated factors among AMI patients using standardized assessment tools. METHODS: Employing a cross-sectional descriptive design, the study involved 210 patients diagnosed with acute myocardial infarction. Participants completed the General Medication Adherence Scale (GMAS), Hospital Anxiety and Depression Scale (HADS), and provided socio-demographic details. RESULTS: The study revealed partial adherence to medications among AMI patients, with mean scores of 24.89 (± 3.64) out of 33. Notably, good adherence was observed in non-adherence due to patient behavior (mean ± SD = 11.8 ± 2.3 out of 15) and additional disease burden (mean ± SD = 8.65 ± 2.21 out of 12), while partial adherence was noted in non-adherence due to financial constraints (mean ± SD = 4.44 ± 1.34 out of 6). Patients reported mild anxiety (mean ± SD = 8.38 ± 2.81) and no depressive symptoms (mean ± SD = 7.43 ± 2.42). Multiple linear regression analysis indicated that employed status, younger age, shorter duration of MI, lower anxiety, and depression levels were associated with higher medication adherence. However, factors such as monthly income, gender, educational level, and marital status did not predict medication adherence. CONCLUSION: The study highlights the significance of addressing anxiety and depression levels and considering socio-demographic factors when designing interventions to enhance medication adherence among AMI patients. Further research is needed to explore additional determinants of medication adherence and develop tailored interventions to improve patient outcomes post-AMI.
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Ansiedad , Depresión , Cumplimiento de la Medicación , Infarto del Miocardio , Humanos , Masculino , Infarto del Miocardio/psicología , Infarto del Miocardio/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Cumplimiento de la Medicación/psicología , Femenino , Persona de Mediana Edad , Estudios Transversales , Ansiedad/psicología , Ansiedad/tratamiento farmacológico , Depresión/psicología , Depresión/tratamiento farmacológico , Anciano , AdultoRESUMEN
BACKGROUND: Depression is often linked to inflammation in the brain. Researchers have been exploring ways to reduce this inflammation to improve depression symptoms. One potential target is a protein called RIPK1, which is known to contribute to brain inflammation. However, it's unclear how RIPK1 influences depression. Our study aims to determine whether RIPK1 inhibition could alleviate neuroinflammation-associated depression and elucidate its underlying mechanisms. METHODS: To investigate our research objectives, we established a neuroinflammation mouse model by administering LPS. Behavioral and biochemical assessments were conducted on these mice. The findings were subsequently validated through in vitro experiments. RESULTS: Using LPS-induced depression models, we investigated RIPK1's role, observing depressive-like behaviors accompanied by elevated cytokines, IBA-1, GFAP levels, and increased inflammatory signaling molecules and NO/H2O2. Remarkably, Necrostatin (Nec-1 S), a RIPK1 inhibitor, mitigated these changes. We further found altered expression and phosphorylation of eIF4E, PI3K/AKT/mTOR, and synaptic proteins in hippocampal tissues, BV2, and N2a cells post-LPS treatment, which Nec-1 S also ameliorated. Importantly, eIF4E inhibition reversed some of the beneficial effects of Nec-1 S, suggesting a complex interaction between RIPK1 and eIF4E in LPS-induced neuroinflammation. Moreover, citronellol, a RIPK1 agonist, significantly altered eIF4E phosphorylation, indicating RIPK1's potential upstream regulatory role in eIF4E and its contribution to neuroinflammation-associated depression. CONCLUSION: These findings propose RIPK1 as a pivotal mediator in regulating neuroinflammation and neural plasticity, highlighting its significance as a potential therapeutic target for depression.
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Depresión , Modelos Animales de Enfermedad , Lipopolisacáridos , Enfermedades Neuroinflamatorias , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Animales , Masculino , Ratones , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Imidazoles/farmacología , Imidazoles/uso terapéutico , Indoles/farmacología , Indoles/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/patología , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacosRESUMEN
The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.
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Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico , Agonistas de los Canales de Calcio , Canales de Calcio Tipo L , Metilación de ADN , ADN Metiltransferasa 3A , Depresión , Metionina , Animales , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo L/efectos de los fármacos , Metionina/farmacología , Masculino , Depresión/tratamiento farmacológico , Depresión/metabolismo , Ratones , Agonistas de los Canales de Calcio/farmacología , Metilación de ADN/efectos de los fármacos , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Ratones Endogámicos C57BL , Antidepresivos/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Lipopolisacáridos/farmacología , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: Chronic diseases, such as hemophilia, can evoke psychological sequelae and be associated with a higher risk of mental health disorders. The utilization of antidepressant and antipsychotic drugs in subjects with hemophilia is not completely understood and few data are available. OBJECTIVES: The aim of this analysis is to describe use of antidepressant and antipsychotic drugs in subjects with hemophilia of the Umbria Region in the period 2011-2022. METHODS: A descriptive, cross-sectional, and retrospective analysis based on data on filled prescriptions for antidepressants and antipsychotics has been carried out. The overall and annual prevalence of drugs use and consumption were calculated based on pharmaceutical prescriptions charged to the National Health Service in subjects with hemophilia and matched controls from general population. RESULTS: In the study period 170 subjects with hemophilia were identified; about 80% were male. About 20% and 8.2% received antidepressants and antipsychotics, respectively. A higher percentage of users and consumption were found in subjects with hemophilia compared to matched controls, although no statistically significant differences were observed. CONCLUSIONS: Our analysis suggests that depression and psychosis are important comorbidities in subjects with hemophilia. Further larger studies are needed in order to confirm these data and better define the burden of mental health disorders in subjects with hemophilia.
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Antidepresivos , Antipsicóticos , Hemofilia A , Humanos , Masculino , Hemofilia A/tratamiento farmacológico , Hemofilia A/epidemiología , Hemofilia A/complicaciones , Antipsicóticos/uso terapéutico , Antidepresivos/uso terapéutico , Estudios Retrospectivos , Adulto , Estudios Transversales , Femenino , Persona de Mediana Edad , Italia/epidemiología , Adulto Joven , Anciano , Depresión/epidemiología , Depresión/tratamiento farmacológico , Adolescente , ComorbilidadRESUMEN
Depression is a debilitating mental illness that severely threatens millions of individuals and public health. Because of the multifactorial etiologies, there is currently no cure for depression; thus, it is urgently imperative to find alternative antidepressants and strategies. Growing evidence underscores the prominent role of oxidative stress as key pathological hallmarks of depression, making oxidative stress a potential therapeutic target. In this study, we report a N-doped carbon dot nanozyme (CDzyme) with excellent antioxidant capacity for treating depression by remodeling redox homeostasis and gut microbiota. The CDzymes prepared via microwave-assisted fast polymerization of histidine and glucose exhibit superior biocompatibility. Benefiting from the unique structure, CDzymes can provide abundant electrons, hydrogen atoms, and protons for reducing reactions, as well as catalytic sites to mimic redox enzymes. These mechanisms collaborating endow CDzymes with broad-spectrum antioxidant capacity to scavenge reactive oxygen and nitrogen species (â¢OH, O2-â¢, H2O2, ONOO-), and oxygen/nitrogen centered free radicals. A depression animal model was established by chronic unpredictable mild stress (CUMS) to evaluate the therapeutic efficacy of CDzymes from the behavioral, physiological, and biochemical index and intestinal flora assessments. CDzymes can remarkably improve depression-like behaviors and key neurotransmitters produced in hippocampus tissues and restore the gut microbiota compositions and the amino acid metabolic functions, proving the potential in treating depression through the intestinal-brain axis system. This study will facilitate the development of intestinal flora dysbiosis nanomedicines and treatment strategies for depression and other oxidative stress related multifactorial diseases.
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Antioxidantes , Carbono , Depresión , Microbioma Gastrointestinal , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Carbono/química , Carbono/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Depresión/tratamiento farmacológico , Ratones , Estrés Oxidativo/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Masculino , Puntos Cuánticos/química , Antidepresivos/farmacología , Antidepresivos/químicaRESUMEN
OBJECTIVE: To investigate the effect of Kaixinsan (KXS, a traditional Chinese medicine formula) for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism. METHODS: Forty female BALB/c mice were randomized equally into control group, model group, and low- and high-dose KXS treatment groups, and in the latter 3 groups, mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage. Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test, and the changes in serum levels of depression-related factors were examined. RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS. The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control. RESULTS: KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models. RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress, lipid metabolism and iron ion binding in the prefrontal cortex. Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice. In SH-SY5Y cells, both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis. CONCLUSION: KXS alleviates adriamycininduced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.
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Depresión , Doxorrubicina , Ferroptosis , Ratones Endogámicos BALB C , Corteza Prefrontal , Animales , Ferroptosis/efectos de los fármacos , Ratones , Depresión/tratamiento farmacológico , Depresión/inducido químicamente , Doxorrubicina/efectos adversos , Femenino , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Línea Celular Tumoral , Conducta Animal/efectos de los fármacos , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismoRESUMEN
Depression is a prevalent and debilitating mental disorder that affects millions worldwide. Current treatments, such as antidepressants targeting the serotonergic system, have limitations, including delayed onset of action and high rates of treatment resistance, necessitating novel therapeutic strategies. Ginsenoside Rc (G-Rc) has shown potential anti-inflammatory and neuroprotective effects, but its antidepressant properties remain unexplored. This study investigated the antidepressant effects of G-Rc in an L-alpha-aminoadipic acid (L-AAA)-induced mouse model of depression, which mimics the astrocytic pathology and neuroinflammation observed in major depressive disorder. Mice were administered G-Rc, vehicle, or imipramine orally after L-AAA injection into the prefrontal cortex. G-Rc significantly reduced the immobility time in forced swimming and tail suspension tests compared to vehicle treatment, with more pronounced effects than imipramine. It also attenuated the expression of pro-inflammatory cytokines (TNF-α, IL-6, TGF-ß, lipocalin-2) and alleviated astrocytic degeneration, as indicated by increased GFAP and decreased IBA-1 levels. Additionally, G-Rc modulated apoptosis-related proteins, decreasing caspase-3 and increasing Bcl-2 levels compared to the L-AAA-treated group. These findings suggest that G-Rc exerts antidepressant effects by regulating neuroinflammation, astrocyte-microglia crosstalk, and apoptotic pathways in the prefrontal cortex, highlighting its potential as a novel therapeutic agent for depression.
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Ácido 2-Aminoadípico , Antidepresivos , Astrocitos , Ginsenósidos , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Ratones , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Ginsenósidos/farmacología , Masculino , Ácido 2-Aminoadípico/farmacología , Depresión/tratamiento farmacológico , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Modelos Animales de Enfermedad , Citocinas/metabolismo , Ratones Endogámicos C57BL , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Apoptosis/efectos de los fármacosRESUMEN
Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1ß, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS.
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Depresión , Dieta Alta en Grasa , Síndrome Metabólico , Extractos Vegetales , Salvia , Animales , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/metabolismo , Síndrome Metabólico/etiología , Dieta Alta en Grasa/efectos adversos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Salvia/química , Depresión/tratamiento farmacológico , Depresión/etiología , Depresión/metabolismo , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos ICRRESUMEN
BACKGROUND: Psychedelic-assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic-assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life-threatening diseases (e.g. cancer). However, these substances are illegal in most countries and have been associated with potential risks. OBJECTIVES: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators (e.g. antidepressants) for treatment of anxiety, depression, and existential distress in people with life-threatening diseases. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers on 30 March 2024. In addition, we undertook reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with no restrictions regarding comorbidity, sex, or ethnicity. Interventions comprised a substance-induced psychedelic experience preceded by preparatory therapeutic sessions and followed by integrative therapeutic sessions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies in the review, which evaluated two different interventions: psychedelic-assisted therapy with classical psychedelics (psilocybin ('magic mushrooms') and lysergic acid diethylamide (LSD)), and psychedelic-assisted therapy with 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'). The studies randomised 149 participants with life-threatening diseases and analysed data for 140 of them. The age range of participants was 36 to 64 years. The studies lasted between 6 and 12 months, and were conducted in outpatient settings in the USA and in Switzerland. Drug companies were not involved in study funding, but funding was provided by organisations that promote psychedelic-assisted therapy. Primary outcomes (at 1 to 12 weeks) Anxiety Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in anxiety when compared to active placebo (or low-dose psychedelic): State Trait Anxiety Inventory (STAI-Trait, scale 20 to 80) mean difference (MD) -8.41, 95% CI -12.92 to -3.89; STAI-State (scale 20 to 80) MD -9.04, 95% CI -13.87 to -4.21; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on anxiety, compared to placebo, is very uncertain: STAI-T MD -14.70, 95% CI -29.45 to 0.05; STAI-S MD -16.10, 95% CI -33.03 to 0.83; 1 study, 18 participants; very low certainty evidence. Depression Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in depression when compared to active placebo (or low-dose psychedelic): Beck Depression Inventory (BDI, scale 0 to 63) MD -4.92, 95% CI -8.97 to -0.87; 4 studies, 112 participants; standardised mean difference (SMD) -0.43, 95% CI -0.79 to -0.06; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on depression, compared to placebo, is very uncertain: BDI-II (scale: 0 to 63) MD -6.30, 95% CI -16.93 to 4.33; 1 study, 18 participants; very low certainty evidence. Existential distress Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) compared to active placebo (or low-dose psychedelic) may result in a reduction in demoralisation, one of the most common measures of existential distress, but the evidence is very uncertain (Demoralisation Scale, 1 study, 28 participants): post treatment scores, placebo group 39.6 (SEM 3.4), psilocybin group 18.8 (3.6), P ≤ 0.01). Evidence from other measures of existential distress was mixed. Existential distress was not measured in people receiving psychedelic-assisted therapy with MDMA. Secondary outcomes (at 1 to 12 weeks) Quality of life When classical psychedelics were used, one study had inconclusive results and two reported improved quality of life, but the evidence is very uncertain. MDMA did not improve quality of life measures, but the evidence is also very uncertain. Spirituality Participants receiving psychedelic-assisted therapy with classical psychedelics rated their experience as being spiritually significant (2 studies), but the evidence is very uncertain. Spirituality was not assessed in participants receiving MDMA. Adverse events No treatment-related serious adverse events or adverse events grade 3/4 were reported. Common minor to moderate adverse events for classical psychedelics were elevated blood pressure, nausea, anxiety, emotional distress, and psychotic-like symptoms (e.g. pseudo-hallucination where the participant is aware they are hallucinating); for MDMA, common minor to moderate adverse events were anxiety, dry mouth, jaw clenching, and headaches. Symptoms subsided when drug effects wore off or up to one week later. Certainty of the evidence Although all six studies had intended to blind participants, personnel, and assessors, blinding could not be achieved as this is very difficult in studies investigating psychedelics. Using GRADE criteria, we judged the certainty of evidence to be low to very low, mainly due to high risk of bias and imprecision (small sample size). AUTHORS' CONCLUSIONS: Implications for practice Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life-threatening disease. Psychedelic-assisted therapy seemed to be well tolerated, with no treatment-emergent serious adverse events reported in the studies included in this review. However, the certainty of evidence is low to very low, which means that we cannot be sure about these results, and they might be changed by future research. At the time of this review (2024), psychedelic drugs are illegal in many countries. Implications for research The risk of bias due to 'unblinding' (participants being aware of which intervention they are receiving) could be reduced by measuring expectation bias, checking blinding has been maintained before cross-over, and using active placebos. More studies with larger sample sizes are needed to reduce imprecision. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing.
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Ansiedad , Depresión , Alucinógenos , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Alucinógenos/uso terapéutico , Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Depresión/terapia , Psilocibina/uso terapéutico , Dietilamida del Ácido Lisérgico/uso terapéutico , Antidepresivos/uso terapéutico , Sesgo , Existencialismo , Placebos/uso terapéutico , Adulto , Distrés Psicológico , Neoplasias/psicologíaRESUMEN
BACKGROUND: People living in care homes often have problems with pain, anxiety and depression. Whether being on analgesia, anxiolytics or antidepressants has any bearing on pain severity and quality of life (QoL) in this population, requires further investigation. OBJECTIVES: (i) to examine the relationship between pain, anxiety and depression and medication use in care home residents and (ii) to compare those on medications to treat pain, anxiety and depression, and those who were not, and associations with pain severity and overall QoL. METHODS: This was a secondary analysis of a randomised controlled trial testing a falls prevention intervention in care homes. We recorded pain, anxiety and depression, QoL measurements and prescribed medication use. RESULTS: In 1589 participants, the mean age was 84.7 years (±9.3 SD), 32.2% were male and 67.3% had a diagnosis of dementia. 54.3% and 53.2% of participants had some level of pain and anxiety or depression respectively, regardless of prescribed medication use. There was a direct association between pain severity and being on any analgesia, opioid analgesia, and antidepressants, but no associations between pain severity and use of paracetamol and anxiolytics. QoL was best for residents with no pain and not on any analgesia, anxiolytics or antidepressants and worst for those with moderate-extreme pain and taking at least two of these classes of medications. CONCLUSION: Many care home residents live with pain, anxiety and depression. Addressing residents' pain may also increase their quality of life, but using medication alone to reach this goal may be inadequate.
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Analgésicos , Ansiolíticos , Antidepresivos , Ansiedad , Depresión , Hogares para Ancianos , Casas de Salud , Dimensión del Dolor , Dolor , Calidad de Vida , Humanos , Masculino , Femenino , Ansiolíticos/uso terapéutico , Anciano , Anciano de 80 o más Años , Antidepresivos/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/psicología , Dolor/diagnóstico , Depresión/tratamiento farmacológico , Depresión/psicología , Depresión/diagnóstico , Ansiedad/psicología , Ansiedad/tratamiento farmacológico , Ansiedad/diagnóstico , Analgésicos/uso terapéutico , Accidentes por Caídas/prevención & control , Accidentes por Caídas/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Ansiedad , Depresión , Emociones , Estrés Psicológico , Humanos , Depresión/tratamiento farmacológico , Depresión/terapia , LibrosRESUMEN
The root of Millettia pulchra (YLS) has been traditionally used as a folk medicine for the treatment of depression and insomnia in the Zhuang nationality of China, and its polysaccharides have potential antidepressant effect. In this study, a novel homogeneous polysaccharide (YLP-1) was purified from the crude polysaccharides of YLS, and it is mainly composed of glucose, arabinose and mannose with molar ratio of 87.25%, 10.77%, and 1.98%, respectively. YLP-1 is a novel α-glucan with the backbone of 1,4-Glcp and branched at C6 of 1,4,6-Glcp to combine 1,4-Manp and 1,5-Araf. The microstructure of YLP-1 displayed a uniform ellipsoidal-like chain morphology and dispersed uniformly in solution. YLP-1 effectively ameliorated depression-like ethological behaviors and restored the decreased catecholamine levels in chronic variable stress (CVS)-induced depression rats. Additionally, it significantly improved the disturbance of gut microbiota induced by CVS stimuli, particularly affecting bacteria that produce short-chain fatty acids (SCFAs), such as bacteria species Lactobacillus spp.. In vitro fermentation study further confirmed that YLP-1 intake could promote SCFAs production by Lactobacillus spp. YLP-1 also mitigated the disruption of tryptophan metabolites in urine and serum. These findings provide evidences for the further development of YLP-1 as a macromolecular antidepressant drug.
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Antidepresivos , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Millettia , Polisacáridos , Triptófano , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Antidepresivos/farmacología , Antidepresivos/química , Masculino , Ratas , Polisacáridos/farmacología , Polisacáridos/química , Millettia/química , Triptófano/metabolismo , Ácidos Grasos Volátiles/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Ratas Sprague-DawleyRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet. AIM OF THE STUDY: Here we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula. MATERIALS AND METHODS: Individual herbs (MC; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested in a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using Western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) was used as a positive control for induction of rapid antidepressant effects. RESULTS: A combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA. CONCLUSION: GMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In the LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity.
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Antidepresivos , Depresión , Medicamentos Herbarios Chinos , Lipopolisacáridos , Enfermedades Neuroinflamatorias , Plasticidad Neuronal , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Antidepresivos/farmacología , Plasticidad Neuronal/efectos de los fármacos , Masculino , Depresión/tratamiento farmacológico , Depresión/inducido químicamente , Ratones , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Paeonia/química , Ratones Endogámicos C57BL , Gardenia/química , Modelos Animales de Enfermedad , Serina-Treonina Quinasas TOR/metabolismo , Conducta Animal/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Depression impairs not only central nervous system, but also peripheral systems of the host. Gut microbiota have been proved to be involved in the pathogenesis of depression. Xiaoyaosan (XYS) has a history of over a thousand years in China for treating depression, dramatically alleviating anxiety, cognitive disorders, and especially gastrointestinal dysfunctions. Yet, it still just scratches the surface of the anti-depression mechanisms of XYS. AIM OF THE STUDY: This study aims to elucidate the mechanism of actions of XYS from the perspective of "microbiota-gut-brain" axis. MATERIALS AND METHODS: We firstly evaluated the effects of XYS on the macroscopic behaviors of depressed rats that induced by chronic unpredictable mild stress (CUMS). Secondly, the effects of XYS on intestinal homeostasis of depressed rats were revealed by using dysbacteriosis model. Subsequently, the underlying mechanisms were demonstrated by 16S rRNA gene sequencing technology and molecular biology methods. Finally, correlation analysis and visualization of the anti-depression effects of XYS were performed from the "microbiota - gut - brain" perspective. RESULTS: Our data indicated that XYS ameliorated the depression-like symptoms of CUMS rats, partly depending on the presence of gut microbiota. Furthermore, we illustrated that XYS reversed CUMS-induced gut dysbiosis of depressed rats in terms of decreasing the Bacteroidetes/Firmicutes ratio and the abundances of Bacteroides, and Corynebacterium, while increasing the abundances of Lactobacillus and Adlercreutzia. The significant enrichment of Bacteroides and the level of lipopolysaccharides (LPS) suggested that depression damaged the immune responses and gut barrier. Mechanistically, XYS significantly down-regulated the expression levels of factors that involved in TLR4/NLRP3 signaling pathway in the colon and brain tissues of depressed rats. In addition, XYS significantly increased the levels of claudin 1 and ZO-1, showing that XYS positively maintained the integrity of gut and blood-brain barriers (BBB). CONCLUSION: Our study offers insights into the anti-depression effects of XYS through a lens of "microbiota-TLR4/NLRP3 signaling pathway-barriers", providing a foundation for enhancing clinical efficiency and enriching drug selection, and contributing to our understanding of the mechanisms of traditional Chinese medicines (TCMs) in treating depression.
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Antidepresivos , Eje Cerebro-Intestino , Depresión , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Lipopolisacáridos , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Sprague-Dawley , Transducción de Señal , Receptor Toll-Like 4 , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Eje Cerebro-Intestino/efectos de los fármacos , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/psicología , Estrés Psicológico/metabolismo , Disbiosis/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Modelos Animales de EnfermedadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Depression is a prevalent stress disorder, yet the underlying physiological mechanisms linking stress to appetite and weight loss remain elusive. While most antidepressants are associated with excessive weight and appetite gain, sertraline (SER) exhibits a lower risk of these side effects. Metacinnabar (ß-HgS), the primary component of Tibetan medicine Zuotai, has been shown to enhance mice's resilience against external stress without causing excessive increases in weight or appetite. However, the precise physiological pathway through which ß-HgS restores appetite and weight in stressed mice remains unclear. AIM OF THE STUDY: The objective of this study is to assess the efficacy of ß-HgS in ameliorating weight loss and appetite suppression induced by pressure stimulation in mice, as well as elucidate its potential mechanisms of action. METHODS: The present study employed chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) as experimental models to simulate environmental stress encountered in daily life. Subsequently, a series of experiments were conducted, including behavior tests, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, as well as metabolomics analysis of hippocampal and intestinal contents. RESULT: Dysregulation of glycerophospholipid metabolism may represent the principal pathway underlying reduced appetite, body weight, neurotransmitter and appetite hormone levels, heightened inflammatory response, hippocampal and rectal tissue damage, as well as altered composition of intestinal microbiota in stressed mice. Following intervention with SER and ß-HgS in stressed mice, the deleterious effects induced by stress can be ameliorated, in which the medium-dose ß-HgS exhibited superior performance. CONCLUSION: The aforementioned research findings suggest that the stress-induced decrease in appetite and body weight in mice may be associated with dysregulation in glycerophospholipid metabolism connecting the gut-brain axis. ß-HgS exhibits potential in ameliorating depressive-like symptoms in mice subjected to stress, while concurrently restoring their body weight and appetite without inducing excessive augmentation. Its therapeutic effect may also be attributed to its ability to modulate glycerophospholipid metabolism status and exert influence on the gut-brain axis.
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Apetito , Microbioma Gastrointestinal , Estrés Psicológico , Animales , Masculino , Estrés Psicológico/tratamiento farmacológico , Ratones , Apetito/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Depresión/tratamiento farmacológico , Antidepresivos/farmacología , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Conducta Animal/efectos de los fármacosRESUMEN
Depression is a global health concern affecting nearly 280 million individuals. It not only imposes a significant burden on economies and healthcare systems but also manifests complex physiological connections and consequences. Agmatine, a putative neuromodulator derived primarily from beneficial gut microbes specially Lactobacillus, has emerged as a potential therapeutic agent for mental health. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of agmatine. Therefore, this study aimed to investigate the potential mechanism of agmatine in antibiotic-induced dysbiosis and depression-like behavior in rats, focusing on its modulation of the gut-brain axis. Depression-like behavior associated with dysbiosis was induced through a seven-day regimen of the broad-spectrum antibiotic, comprising ampicillin and metronidazole and validated through microbial, biochemical, and behavioral alterations. On day 8, antibiotic-treated rats exhibited loose fecal consistency, altered fecal microbiota, and depression-like behavior in forced swim test. Pro-inflammatory cytokines were elevated, while agmatine and monoamine levels decreased in the hippocampus and prefrontal cortex. Antibiotic administration disrupted tight junction proteins in the ileum, affecting gut architecture. Oral administration of agmatine alone or combined with probiotics significantly reversed antibiotic-induced dysbiosis, restoring gut microbiota and mitigating depression-like behaviors. This intervention also restored neuro-inflammatory markers, increased agmatine and monoamine levels, and preserved gut integrity. The study highlights the regulatory role of endogenous agmatine in the gut-brain axis in broad-spectrum antibiotic induced dysbiosis and associated depression-like behavior.
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Agmatina , Conducta Animal , Eje Cerebro-Intestino , Depresión , Disbiosis , Microbioma Gastrointestinal , Animales , Agmatina/farmacología , Agmatina/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/metabolismo , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Conducta Animal/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Antibacterianos/farmacología , Ratas Sprague-Dawley , Probióticos/farmacología , Probióticos/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Citocinas/metabolismo , Ampicilina/farmacología , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Depression and dementia represent significant health challenges in older adults. Despite guidelines recommending antidepressants, their efficacy in depressed patients with dementia remains undetermined. OBJECTIVE: This review, in following a living systematic review approach, primarily aims to determine the effect of any-type antidepressant on the level of depressive symptoms in older adults with dementia and secondly if there is an effect of any-type antidepressants on cognitive state, quality of life, and functionality in the old-age population with dementia. METHODS: Systematic review and meta-analysis of RCTs from Medline, Embase, and Cochrane Register. Participants were ≥65 years, with both depression and any type of dementia. Certainty-of-Evidence was assessed through the Cochrane Risk-of-Bias tool and GRADE. Analysis involved standardized mean difference, with 95 % confidence-intervals (CIs). FINDINGS: Of the 27,771 screened articles, 8 studies (617 participants), treated with SSRI, SSNRI, atypical, and tricyclic antidepressants were retained for quantitative synthesis. No evidence for an effect was found (SMD -0.10 [-0.26, 0.07]), nor when subgrouped based on depression severity or dementia level, nor for secondary outcomes. INTERPRETATION: This review did not find evidence of a clinical effect of antidepressants for treating depression in older adults with dementia. Methodological challenges might contribute to this finding.
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Antidepresivos , Demencia , Depresión , Humanos , Demencia/tratamiento farmacológico , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Anciano , Anciano de 80 o más AñosRESUMEN
Constipation is a common symptom in patients with Parkinson's disease (PD) and is often associated with depression. Enteric glial cells (EGCs) are crucial for regulating intestinal inflammation and colon motility, and their activation can lead to the death of intestinal neurons. Glial cell line-derived neurotrophic factor (GDNF) has been recognized for its neuroprotective properties in various neurological disorders, including PD. This study explores the potential of GDNF in alleviating intestinal reactive gliosis and inflammation, thereby improving constipation and depressive behavior in a rat model of PD. A PD model was established via unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA). Five weeks post-injury, AAV5-GDNF (2 ~ 5 × 10^11) was intraperitoneally injected into experimental and control rats. Fecal moisture percentage (FMP) and colonic propulsion rate (CPPR) were used to evaluate colon motility. Colon-related inflammation and colonic epithelial morphology were assessed, and depressive behavior was analyzed one week before sampling. PD rats exhibited reduced colonic motility and GDNF expression, along with increased EGC reactivity and elevated levels of pro-inflammatory cytokines IL-1, IL-6, and TNF-α. Additionally, there was an up-regulation of CX43 and a decrease in PGP 9.5 expression. The intraperitoneal injection of AAV-GDNF significantly protected colonic neurons by inhibiting EGC activation and down-regulating CX43. This treatment also led to a notable reduction in depressive-like symptoms in PD rats with constipation. GDNF effectively reduces markers of reactive gliosis and inflammation, and promotes the survival of colonic neurons, and improves colonic motility in PD rats by regulating CX43 activity. Furthermore, GDNF treatment alleviates depressive behavior, suggesting that GDNF or its agonists could be promising therapeutic agents for managing gastrointestinal and neuropsychiatric symptoms associated with PD.