Traditional Chinese medicine decoctions and Chinese patent medicines for the treatment of depression: Efficacies and mechanisms

Journal of Ethnopharmacology, Год журнала: 2023, Номер 307, С. 116272 - 116272

Опубликована: Фев. 13, 2023

Язык: Английский

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Perturbation-theory machine learning for mood disorders: virtual design of dual inhibitors of NET and SERT proteins

BMC Chemistry, Год журнала: 2025, Номер 19(1)

Опубликована: Янв. 2, 2025

Abstract Mood disorders affect the daily lives of millions people worldwide. The search for more efficient therapies mood remains an active field research. In silico approaches can accelerate inhibitors against protein targets related to disorders. Here, we developed first model perturbation-theory machine learning based on a multiplayer perceptron network (PTML-MLP) simultaneous prediction and design virtual dual-target two proteins associated with disorders, namely norepinephrine serotonin transporters (NET SERT, respectively). PTML-MLP had accuracy around 80%. From chemical point view, could accurately identify both single- present in dataset used build it. Through application fragment-based topological (FBTD) approach, molecular descriptors (multi-label graph-based indices) were physicochemically structurally interpreted. Such interpretations enabled (a) extraction different fragments positive influence enhancement activity (b) four new drug-like molecules by assembling (fusing and/or connecting) several suitable fragments. designed predicted exhibit NET SERT proteins. These predictions, together estimated druglikeness suggest that be promising chemotypes considered future synthesis biological experimentation context treatments

Язык: Английский

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Clinical specificity profile for novel rapid acting antidepressant drugs

International Clinical Psychopharmacology, Год журнала: 2023, Номер 38(5), С. 297 - 328

Опубликована: Июнь 29, 2023

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants not effective in all patients and often show a relevant response latency, range of adverse events, including weight gain sexual dysfunction. Novel rapid agents were developed the aim overcoming at least part these issues. drugs target glutamate, gamma-aminobutyric acid, orexin, other receptors, providing broader pharmacodynamic mechanisms, that is, expected to increase possibility personalizing treatments on individual profile. These new combining action, tolerable profile, higher effectiveness specific symptoms, which relatively poorly targeted by standard antidepressants, such as anhedonia reward, suicidal ideation/behaviours, insomnia, cognitive deficits, irritability. This review discusses specificity profile namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), zuranolone (SAGE-217). The main is provide an overview efficacy/tolerability compounds mood having different symptom/comorbidity patterns, help clinicians optimization risk/benefit ratio when prescribing drugs.

Язык: Английский

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Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis

Pharmaceuticals, Год журнала: 2025, Номер 18(5), С. 702 - 702

Опубликована: Май 9, 2025

Background/Objective: Major depressive disorder (MDD) is a common mental disorder, with significant portion of patients developing treatment-resistant depression (TRD). Esketamine an antagonist the N-methyl-D-aspartate receptor indicated as nasal spray in combination other antidepressants for adults TRD. Signals suspected adverse reactions (SARs) to esketamine from EudraVigilance database European countries were analyzed more defined safety profile this drug real world. Methods: SARs reported data system analyzed, and disproportionality analysis indicating suicidality esketamine, comparison fluoxetine venlafaxine, was performed. Results: Increases blood pressure (15.4%) dissociation (15.0%) most frequently SARs. The sex distribution indicates prevalence women, except increased completed suicide, which signaled men, while (18–64 years) elders (65–85 ages largest number esketamine. results indicate existence potential increase risk suicide depressed taking when compared venlafaxine. Conclusions: Apart carefulness due known limitations pharmacovigilance research conducted by using systems spontaneous signals SARs, points toward need greater attention being paid following prescription subjects. In regard, regulatory agencies also recommend, history suicide-related events or those exhibiting degree suicidal ideation prior beginning treatment should receive careful monitoring during treatment.

Язык: Английский

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The role of polyunsaturated fatty acids in neuronal signaling in depression and cognitive processes

Archives of Biochemistry and Biophysics, Год журнала: 2023, Номер 737, С. 109555 - 109555

Опубликована: Фев. 24, 2023

Язык: Английский

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Advancements Exploring Major Depressive Disorder: Insights on Oxidative Stress, Serotonin Metabolism, BDNF, HPA Axis Dysfunction, and Pharmacotherapy Advances

International Journal of Translational Medicine, Год журнала: 2024, Номер 4(1), С. 176 - 196

Опубликована: Март 5, 2024

Major depressive disorder (MDD), a prevalent mental illness, is marked by complex mixture of biological factors. This review focuses on the roles oxidative stress, tryptophan-serotonin metabolism, brain-derived neurotrophic factor (BDNF), and hypothalamic–pituitary–adrenal (HPA) axis in MDD’s pathophysiology. Oxidative defined as an imbalance between pro-oxidants antioxidants, closely linked to neurobiological changes. The tryptophan (TRP)-/serotonin (5-HT) metabolic pathway also known be crucial mood regulation, with its dysregulation being central aspect MDD. Additionally, BDNF, key for neuronal growth plasticity, often shows alterations MDD patients, supporting role disorder’s progression. Furthermore, HPA axis, which manages stress response, frequently disrupted MDD, further contributing pathology. In addition exploring these mechanisms, this explores pharmacotherapy including new advances. These advancements treatment strategies are managing effectively. Understanding mechanisms latest pharmacological interventions essential developing more effective treatments

Язык: Английский

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A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 4, 2024

Abstract Background Neuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- anxiety-like disorders. In recent years, there has been significant attention on natural compounds with potent anti-inflammatory effects due to their potential mitigating neuroinflammation neuroplasticity. Methods the present study, we aimed evaluate neuroprotective oleacein (OC), rare secoiridoid derivative found extra virgin olive oil. Our goal was explore BDNF/TrkB neurotrophic activity OC subsequently assess its for modulating neuroinflammatory response using human neuroblastoma cells (SH-SY5Y cells) an vivo model depression induced by lipopolysaccharide (LPS)-mediated inflammation. Results SH-SY5Y cells, exhibited dose-dependent increase BDNF expression. This enhancement absent when were co-treated inhibitors BDNF's receptor TrkB, well downstream molecules PI3K MEK. Whole-transcriptomics analysis revealed that upregulated cell cycle-related genes under normal conditions, while downregulating inflammation-associated LPS-induced conditions. Furthermore, surface plasmon resonance (SPR) assays demonstrated stronger more stable binding affinity TrkB compared positive control, 7,8-dihydroxyflavone. Importantly, bioluminescence imaging single oral dose significantly increased expression brains Bdnf-IRES-AkaLuc mice. administration at dosage 10 mg/kg body weight days reduced immobility time tail suspension test LPS-treated group. RT-qPCR decreased pro-inflammatory cytokines Tnfα , Il6 Il1β simultaneously enhancing Bdnf expression, both pro mature protein levels mice hippocampus. These changes comparable those control antidepressant drug fluoxetine. Additionally, microarray mouse confirmed could counteract inflammatory biological events. Conclusion Altogether, our study represents first report antineuroinflammatory properties via modulation activity. finding underscores therapeutic agent anxiety-related

Язык: Английский

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A novel rat model of cerebral small vessel disease based on vascular risk factors of hypertension, aging, and cerebral hypoperfusion

Hypertension Research, Год журнала: 2024, Номер 47(8), С. 2195 - 2210

Опубликована: Июнь 13, 2024

Язык: Английский

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The effects of physical activity on glutamate neurotransmission in neuropsychiatric disorders

Frontiers in Sports and Active Living, Год журнала: 2023, Номер 5

Опубликована: Март 6, 2023

Physical activity (PA) is an effective way of increasing cognitive and emotional health counteracting many psychiatric conditions. Numerous neurobiological models for depression have emerged in the past 30 years but struggle to incorporate effects exercise. The hippocampus pre-frontal cortex (PFC) containing predominantly glutamate neurotransmission, are centres changes seen depression. There therefore interest glutamatergic systems which offers new paradigms understanding mechanisms connecting physical activity, stress, inflammation depression, not explained by serotonin theories Similar hippocampal dysfunction observed other neuropsychiatric Excitatory neurones high functionality, also ATP requirements vulnerable glucocorticoid or pro-inflammatory stress that causes mitochondrial dysfunction, with synaptic loss, culminating depressed mood cognition. Exercise improves function, angiogenesis synaptogenesis. Within hypothesis been extensively researched, PA as a mitigator less understood. This review examines underlying evidence interventions within this framework. A dynamic glutamate-based homeostatic model suggested whereby neuroinflammation form counterbalancing influences on cell manifests conditions when homeostasis disrupted.

Язык: Английский

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Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression

Pharmaceutical Biology, Год журнала: 2023, Номер 61(1), С. 1414 - 1430

Опубликована: Сен. 9, 2023

Crocin exhibits anti-depressant properties. However, its underlying mechanisms and relationship with metabolomics remain unclear.This study elucidates the mechanism of action potential targets crocin in treating chronic unexpected mild stress (CUMS)-induced depression rats.Male Sprague-Dawley (SD) rats underwent 4 weeks CUMS to establish model. The normal control (distilled water), (25 mg/kg), fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated effects crocin, while liquid chromatography-mass spectrometry identified differential metabolites their associated metabolic pathways. Subsequently, network pharmacology was utilized predict crocin.Crocin significantly increased body weight (from 319.16 ± 4.84 g 325.67 2.84 g), sucrose preference 0.46 0.09 0.70 0.09), vertical activity 2.83 1.94 8 2.36), horizontal 1 0.63 4.5 3.08) decreased immobilization time 13.16 2.69 3.97 3.00). Metabolomics analysis 7 5 From combined metabolomics, three (PRMT1, CYP3A4, GLB1) are overlapping two most important pathways tryptophan metabolism glycerolipid metabolism.This provides insights into antidepressant therapeutic effect mechanisms. findings contribute a better understanding involved establishing strong foundation future research this area.

Язык: Английский

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