Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 280 - 280

Published: Jan. 27, 2023

Neurological and neurodegenerative diseases, particularly those related to aging, are on the rise, but drug therapies rarely curative. Functional disorders organic degeneration of nervous tissue often have complex causes, in which phenomena oxidative stress, inflammation cytotoxicity intertwined. For these reasons, search for natural substances that can slow down or counteract pathologies has increased rapidly over last two decades. In this paper, studies neuroprotective effects flavonoids (especially most widely used, hesperidin quercetin) animal models depression, neurotoxicity, Alzheimer’s disease (AD) Parkinson’s reviewed. The literature topics amounts a few hundred publications vitro vivo (notably rodents) provides us with very detailed picture action mechanisms targets substances. These include decrease enzymes produce reactive oxygen ferroptosis, inhibition mono-amine oxidases, stimulation Nrf2/ARE system, induction brain-derived neurotrophic factor production and, case AD, prevention amyloid-beta aggregation. neuroinflammatory processes been documented as cytokine formation (mainly TNF-alpha IL-1beta) by microglia astrocytes, modulating number regulatory proteins such Nf-kB NLRP3/inflammasome. Although clinical trials humans still scarce, preclinical allow consider hesperidin, quercetin, other interesting safe dietary molecules be further investigated complementary treatments order prevent diseases moderate their deleterious effects.

Language: Английский

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Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Nov. 27, 2023

As one of most common and severe mental disorders, major depressive disorder (MDD) significantly increases the risks premature death other medical conditions for patients. Neuroinflammation is abnormal immune response in brain, its correlation with MDD receiving increasing attention. has been reported to be involved through distinct neurobiological mechanisms, among which dysregulation neurogenesis dentate gyrus (DG) hippocampus (HPC) The DG two niches adult mammalian neurotrophic factors are fundamental regulators this process. cell types mediating neuroinflammation include microglia, astrocytes, oligodendrocytes, meningeal leukocytes, peripheral cells selectively penetrate blood-brain barrier infiltrate into inflammatory regions. This review summarizes functions affected by during progression corresponding influences on memory patients model animals.

Language: Английский

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Gut microbiota changes require vagus nerve integrity to promote depressive-like behaviors in mice

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(7), P. 3002 - 3012

Published: May 2, 2023

Chronic stress constitutes a major risk factor for depression that can disrupt various aspects of homeostasis, including the gut microbiome (GM). We have recently shown GM imbalance affects adult hippocampal (HPC) neurogenesis and induces depression-like behaviors, with exact mechanisms being under active investigation. Here we hypothesized vagus nerve (VN), key bidirectional route communication between brain, could relay effects stress-induced changes on HPC plasticity behavior. used fecal samples derived from mice sustained unpredictable chronic mild (UCMS) to inoculate healthy assess standard behavioral readouts anxiety- depressive-like behavior, conduct histological molecular analyses evaluate neurotransmission pathways neuroinflammation. To study potential role VN in mediating brain functions subdiaphragmatic vagotomy (Vx) prior transfer. found inoculation UCMS activates early both serotonin dopamine brainstem HPC. These are associated prompt persistent deficits induce neuroinflammatory responses Remarkably, Vx abrogates deficits, neuroinflammation suggesting vagal afferent necessary drive GM-mediated brain.

Language: Английский

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Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Jan. 4, 2022

Abstract Patients with inflammatory bowel disease (IBD) suffer from depression at higher rates than the general population. An etiological trigger of depressive symptoms is theorised to be inflammation within central nervous system. It believed that heightened intestinal and dysfunction enteric system (ENS) contribute impaired permeability, which facilitates translocation enterotoxins into blood circulation. Consequently, these may compromise immunological physiological functioning distant non-intestinal tissues such as brain. In vivo models colitis provide evidence increased blood–brain barrier permeability enhanced (CNS) immune activity triggered by blood-borne mediators. Understanding immunological, physiological, structural changes associated IBD neuroinflammation aid in development more tailored suitable pharmaceutical treatment for IBD-associated depression.

Language: Английский

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Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: March 1, 2023

Neuroinflammation has been suggested that affects the processing of depression. There is renewed interest in berberine owing to its anti-inflammatory effects. Herein, we investigated whether attenuate depressive-like behaviors via inhibiting NLRP3 inflammasome activation mice model depression.Adult male C57BL/6N were administrated corticosterone (CORT, 20 mg/kg/day) for 35 days. Two doses (100 mg/kg/day and 200 orally from day 7 until 35. Behavioral tests performed measure depression-like alterations. Differentially expressed gene analysis was RNA-sequencing data prefrontal cortex. measured by quantitative reverse transcription polymerase chain reaction, western blotting, immunofluorescence labeling. The neuroplasticity synaptic function labeling, Golgi-Cox staining, transmission electron microscope, whole-cell patch-clamp recordings.The results behavioral demonstrated attenuated induced CORT. identified markedly upregulated after long-term CORT exposure. Berberine reversed concentrations peripheral brain cytokines, elicited cortex hippocampus decreased berberine. In addition, lower frequency neuronal excitation as well dendritic spine reduction treatment. Together, increases hippocampal adult neurogenesis plasticity CORT.The anti-depressants effects accompanied reduced neuroinflammatory response rescued deterioration suppression impairments neurogenesis.

Language: Английский

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Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 423 - 423

Published: Feb. 28, 2024

The involvement of central and peripheral inflammation in the pathogenesis prognosis major depressive disorder (MDD) has been demonstrated. increase pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, IL-18, TNF-α) individuals with depression may elicit neuroinflammatory processes inflammation, mechanisms that, turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation dysbiosis induce alterations tryptophan metabolism, culminating decreased serotonin synthesis, impairments neuroplasticity-related mechanisms, glutamate-mediated excitotoxicity. This review aims highlight inflammatory (neuroinflammation, dysbiosis) involved pathophysiology MDD explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines evidence have indicated that addition antidepressants, physical exercise, probiotics, nutraceuticals (agmatine, ascorbic acid, vitamin D) possess effects their antidepressant properties. Further studies are necessary benefits these alternative therapies MDD.

Language: Английский

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Molecular Mechanisms of Neurogenic Inflammation of the Skin

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 5001 - 5001

Published: March 5, 2023

The skin, including the hypodermis, is largest body organ and in constant contact with environment. Neurogenic inflammation result of activity nerve endings mediators (neuropeptides secreted by development inflammatory reaction skin), as well interactions other cells such keratinocytes, Langerhans cells, endothelial mast cells. activation TRPV–ion channels results an increase calcitonin gene-related peptide (CGRP) substance P, induces release pro-inflammatory contributes to maintenance cutaneous neurogenic (CNI) diseases psoriasis, atopic dermatitis, prurigo rosacea. Immune present skin (mononuclear dendritic cells) also express TRPV1, their directly affects function. TRPV1 mediates communication between sensory immune increasing (cytokines neuropeptides). Understanding molecular mechanisms underlying generation, modulation neuropeptide neurotransmitter receptors can aid effective treatments for disorders.

Language: Английский

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JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Nov. 8, 2023

Abstract The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological pathological processes such inflammation stress. Dysregulation this can lead to severe immunodeficiencies malignancies, its role extends neurotransduction pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological inflammatory disorders, their application has generally been limited diseases with similar pathogenic features. Despite the modest expression of JAK-STAT CNS, it is crucial for functions cortex, hippocampus, cerebellum, making relevant conditions like Parkinson's disease other neuroinflammatory disorders. Furthermore, influence on serotonin receptors phospholipase C implications stress mood This review expands understanding JAK-STAT, moving beyond traditional contexts explore stress-related disorders CNS function. Recent findings, effectiveness Jakinibs chronic rheumatoid arthritis, expand therapeutic applicability. Advances isoform-specific inhibitors, including filgotinib upadacitinib, promise greater specificity fewer off-target effects. Combination therapies, involving monoclonal antibodies, aiming enhance efficacy also give great hope. Overall, bridges gap between basic science clinical application, elucidating complex human health guiding future interventions. Graphical

Language: Английский

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Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 688 - 688

Published: Feb. 22, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae SARS-CoV-2 (PASC), referred to as “Long-COVID,” characterized by persistent physical mental fatigue. However, exact pathogenetic mechanisms affecting brain are still not well-understood. There is increasing evidence neurovascular inflammation in brain. precise role neuroinflammatory response that contributes severity long COVID pathogenesis clearly understood. Here, we review reports spike protein can cause blood–brain barrier (BBB) dysfunction damage neurons either directly, or via activation mast cells microglia release various molecules. Moreover, provide recent novel flavanol eriodictyol particularly suited for development an effective treatment alone together with oleuropein sulforaphane (ViralProtek®), all which have potent anti-viral anti-inflammatory actions.

Language: Английский

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Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial

Journal of Psychiatry and Neuroscience, Journal Year: 2023, Volume and Issue: 48(1), P. E23 - E33

Published: Jan. 18, 2023

Background:

In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing symptoms depression needed. As the gut microbiota–brain axis is linked and cognition, we investigated effect of a 4-week high-dose probiotic supplementation on depression.

Methods:

This randomized controlled trial included 60 patients with MDD, whom 43 entered modified intention-to-treat analysis. A supplement or indistinguishable placebo containing maltose was administered over 31 days addition as usual for Participant scores Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, both Trail Making versions well brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after 4 weeks intervention. Additionally, brain activation changes during working memory processing before

Results:

We found significantly improved immediate recall VLMT group intervention, trend × interaction considering all points. Furthermore, hippocampus processing, revealing remediated function group. Other measures did not reveal significant changes.

Limitations:

The modest sample size resulting from our exclusion low-compliant cases should be considered.

Conclusion:

Additional enhances verbal episodic affects neural mechanisms underlying impaired cognition MDD. present findings support importance MDD emphasize potential microbiota-related regimens treat

Clinical registration:

clinicaltrials.gov identifier NCT02957591.

Language: Английский

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