Drug repurposing may generate novel approaches to treating depression

Ebada, Mohamed Elsaed

doi:10.1111/jphp.12815

Cited by 30 publications

(31 citation statements)

References 111 publications

(236 reference statements)

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“…The elevated release of cytokines observed with neuroinflammation also drives glutamatergic neurotransmission inducing excitotoxicity and consequently neuronal death (Haroon et al, 2014). Although neuroinflammation is not specific to depression, it does account for a large part of its pathophysiology and anti-inflammatory medication has been successful in alleviating some depressive symptoms (Kohler et al, 2014; Ebada, 2017). As previously described, stress is a major risk factor for depression and neuroinflammation could explain, in part, how stress induces the psychological impairment characteristic of depression.…”

Section: Gut-brain-axis Mechanisms Linking Polyphenolic Microbial Metmentioning

confidence: 99%

The Gut Microbiota Links Dietary Polyphenols With Management of Psychiatric Mood Disorders

Westfall

Pasinetti

2019

Front. Neurosci.

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The pathophysiology of depression is multifactorial yet generally aggravated by stress and its associated physiological consequences. To effectively treat these diverse risk factors, a broad acting strategy is required and is has been suggested that gut-brain-axis signaling may play a pinnacle role in promoting resilience to several of these stress-induced changes including pathogenic load, inflammation, HPA-axis activation, oxidative stress and neurotransmitter imbalances. The gut microbiota also manages the bioaccessibility of phenolic metabolites from dietary polyphenols whose multiple beneficial properties have known therapeutic efficacy against depression. Although several potential therapeutic mechanisms of dietary polyphenols toward establishing cognitive resilience to neuropsychiatric disorders have been established, only a handful of studies have systematically identified how the interaction of the gut microbiota with dietary polyphenols can synergistically alleviate the biological signatures of depression. The current review investigates several of these potential mechanisms and how synbiotics, that combine probiotics with dietary polyphenols, may provide a novel therapeutic strategy for depression. In particular, synbiotics have the potential to alleviate neuroinflammation by modulating microglial and inflammasome activation, reduce oxidative stress and balance serotonin metabolism therefore simultaneously targeting several of the major pathological risk factors of depression. Overall, synbiotics may act as a novel therapeutic paradigm for neuropsychiatric disorders and further understanding the fundamental mechanisms of gut-brain-axis signaling will allow full utilization of the gut microbiota’s as a therapeutic tool.

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Section: Gut-brain-axis Mechanisms Linking Polyphenolic Microbial Metmentioning

confidence: 99%

The Gut Microbiota Links Dietary Polyphenols With Management of Psychiatric Mood Disorders

Westfall

Pasinetti

2019

Front. Neurosci.

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“…Most of the currently used antidepressants primarily affect monoaminergic (i.e., serotonin or 5-hydroxytryptamine, 5HT; noradrenaline, NA; dopamine, DA) neurotransmission ( 5 ), and scarce progress has been made over the last several years to develop novel antidepressant drugs. An innovative and promising approach favours instead the repurposing of existing medication with a well-defined safety profile and capable of targeting emerging physiopathological pathways implicated in depression ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

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Background: Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.Methods: We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.Results: Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.Limitations: We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.Conclusions: Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.

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“…erefore, paying attention to the physical and mental health of athletes and taking effective measures in time for prevention and treatment have very important practical significance for the athletes and the society. Traditionally, the most common treatment methods of depression include the drug treatment and psychological treatment [6,7]. Drug treatment has a certain degree of dependence and cannot cure it, which is obviously not suitable for athletes.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Hyperbaric Oxygen Combined with Virtual Reality Training on Oxidative Stress Indicators and Inflammatory Factors of Swimming Athletes Suffering from Depression

Zhang

et al. 2021

Journal of Healthcare Engineering

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This study was conducted to explore the effect of hyperbaric oxygen (HBO) therapy combined with virtual reality (VR) training on oxidative stress indicators (OSIs) and inflammatory factors (IFs) in swimming athletes with depression. 88 swimming athletes suffering from depression were grouped into a control group (group C) and a research group (group R). The patients in group C were given HBO therapy, and the group R was given HBO therapy combined with VR training. The Physical Health Questionnaire (PHQ-9) and the Symptom Checklist (SCL-90) were adopted to assess the depression status of patients. The differences between the two groups of serum OSIs and IFs before and after the intervention were compared and analyzed. The results disclosed that the PHQ-9 score and SCL-90 score in group R were not different from those in group C before the intervention, but those in group R were greatly decreased in contrast to group C after the intervention ( P < 0.05 ). Before the intervention, there was no obvious difference in the OSIs and the IFs between the two groups. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in the two groups were decreased greatly after intervention, and those in the group R were much lower than those in group C ( P < 0.05 ). Compared with the preintervention, the levels of malondialdehyde (MDA) in both groups were reduced observably, and the levels of superoxide dismutase (SOD), nitric oxide (NO), and glutathione peroxidase (GSH-Px) were dramatically increased. The MDA in group R was much lower, while the SOD, NO, and GSH-Px were much higher in contrast to group C ( P < 0.05 ). It indicated that HBO combined with VR training had a good clinical effect for swimming athletes suffering from depression, and it could reduce the oxidative stress and inflammation, thereby helping patients recover quickly.

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Drug repurposing may generate novel approaches to treating depression

Abstract: Drug repurposing represents an alternative approach to cope with major obstacles, including financial insufficiency and unavoidable long lag evaluation time, undermining the classical pathway of developing new hit compounds into clinically approved antidepressants.

Cited by 30 publications

References 111 publications

The Gut Microbiota Links Dietary Polyphenols With Management of Psychiatric Mood Disorders

The Gut Microbiota Links Dietary Polyphenols With Management of Psychiatric Mood Disorders

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

The Effect of Hyperbaric Oxygen Combined with Virtual Reality Training on Oxidative Stress Indicators and Inflammatory Factors of Swimming Athletes Suffering from Depression

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