Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 30, 2023

Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis poorly understood. The heritability estimate of MDD 30-40%, suggesting genetics alone do not account for most the risk major depression. Another factor known to associate with involves environmental stressors such as childhood adversity recent life stress. Recent studies have emerged show biological impact factors in other stress-related disorders mediated by variety epigenetic modifications. These modification alterations contribute abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission neuroglia dysfunction, which are involved pathophysiology MDD. Furthermore, marks been associated diagnosis treatment evaluation modifications holds promise further understanding heterogeneous etiology complex phenotypes MDD, may identify new therapeutic targets. Here, we review preclinical clinical findings, including DNA methylation, histone modification, noncoding RNA, RNA chromatin remodeling In addition, elaborate on contribution these mechanisms pathological trait variability depression discuss how can be exploited purposes.

Language: Английский

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An Overview of Cannabidiol as a Multifunctional Drug: Pharmacokinetics and Cellular Effects

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 473 - 473

Published: Jan. 18, 2024

Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive review delves into the complex pharmacokinetics of CBD, including factors such as bioavailability, distribution, safety profile, and dosage recommendations, which contribute to compound’s pharmacological profile. CBD’s role inhibitor is explored, encompassing interactions with endocannabinoid system ion channels. The anti-inflammatory effects, influencing Interferon-beta NF-κB, position it versatile candidate immune regulation interventions in inflammatory processes. historical context Sativa’s use recreational medicinal purposes adds depth discussion, emphasizing emergence pivotal phytocannabinoid. As research continues, integration clinical practice holds promise revolutionizing treatment approaches enhancing patient outcomes. evolution CBD encourages ongoing exploration, offering prospect unlocking new utility.

Language: Английский

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Exploring the Anxiolytic, Antidepressant, and Immunomodulatory Effects of Cannabidiol in Acute Stress Rat Models

Applied Biosciences, Journal Year: 2025, Volume and Issue: 4(1), P. 4 - 4

Published: Jan. 21, 2025

Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, is believed to have anxiety-reducing and antidepressant effects. However, existing data are inconsistent, likely due variations in experimental designs, dosages, stress models. This study sought assess the impact of CBD on anxiety depression-like behaviors Wistar rats exposed acute cold stress, as well its pro- anti-inflammatory cytokines. Male were treated with (2.5, 5, or 10 mg/kg) vehicle for 14 days subjected behavioral tests, including elevated plus maze, social interaction, forced swim tests. Serum levels cytokines (IL-6, TNF-α, IL-1β, IL-10) analyzed post-experiment using ELISA. Results demonstrated dose-dependent anxiolytic effect CBD, significant improvements interaction reductions anxiety-like at 5 mg/kg. All doses decreased immobility test, suggesting Furthermore, selectively lowered IL-6 levels, key cytokine depression pathogenesis. These findings indicate that has properties, partially mediated by modulation inflammatory processes, particularly IL-6.

Language: Английский

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Cannabidiol (CBD) potentiates physiological and behavioral markers of hypothalamic–pituitary–adrenal (HPA) axis responsivity in female and male mice

Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Language: Английский

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Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain

Drugs, Journal Year: 2021, Volume and Issue: 81(13), P. 1513 - 1557

Published: Sept. 1, 2021

The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body evidence suggests that phytocannabinoids are beneficial range conditions. At the same time impressing development observed formulations delivery systems expanding potential use cannabinoids as an effective therapy. objective this review is to present most results from pharmaceutical companies groups investigating methods improve cannabinoid bioavailability clearly establish its therapeutic efficacy, dose ranges, safety also patient compliance. Particular focus application pain treatment, describing principal employed, promising each administration routes updating clinical evaluations. To offer reader wider view, discusses formulation starting galenic preparation up nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, data meta-analysis used different management summarized, evaluating their real effectiveness, order spare opioids patients' quality life. Promising treatments other important pathologies reviewed likely future directions formulations.

Language: Английский

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Promising Nanocarriers to Enhance Solubility and Bioavailability of Cannabidiol for a Plethora of Therapeutic Opportunities

Molecules, Journal Year: 2022, Volume and Issue: 27(18), P. 6070 - 6070

Published: Sept. 17, 2022

In recent years, the interest in cannabidiol (CBD) has increased because of lack psychoactive properties. However, CBD low solubility and bioavailability, variable pharmacokinetics profiles, poor stability, a pronounced presystemic metabolism. nanoformulations include nanosuspensions, polymeric micelles nanoparticles, hybrid nanoparticles jelled cross-linked chitosan, numerous nanosized lipid formulations, including nanostructured carriers, vesicles, SNEEDS, nanoemulsions, microemulsions. Nanoformulations have resulted high solubility, encapsulation efficiency, sustained release. Some studies assessed Cmax AUC decreased Tmax. A rational evaluation reported this review evidences how some them are very preliminary should be completed before performing clinical trials. Almost all developed simple architectures, well-known safe nanocarriers, or even nanosuspensions. addition, conventional routes administration generally investigated. As consequence, many these almost ready for forthcoming translations. nanosystems promising plethora therapeutic opportunities versatility terms release, crossing physiological barriers, number possible administration.

Language: Английский

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Citrus limon L. (lemon) seed extract shows neuro-modulatory activity in an in vivo thiopental-sodium sleep model by reducing the sleep onset and enhancing the sleep duration

Journal of Integrative Neuroscience, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 28, 2022

Citrus limon L. is an ingenious alternative medication and has a broad scope in managing several health conditions as part of natural remedies. Recently, medicinal plants have witnessed incredible consideration worldwide the field neuroscience for remedial intervention. The present work investigated phytochemical compounds neuropharmacological potential seed extract step to partially validate its formulations nutraceuticals using vivo model. Diverse groups such alkaloids, glycosides, flavonoids, tannins, gums, saponins, steroids were qualitatively identified through colorimetric methods utilizing standard compounds. properties studied Swiss albino mice with sleep time induced by thiopental sodium taken end-point, hole cross, board, open-field experiments at varying doses 50 100 mg/kg body weight. Phytochemical screening showed that steroids, glycosides are aqueous seed. extracts demonstrated significant reduction onset enhanced duration dose-dependent manner sodium-induced sleeping time, along marked decrease unconstrained locomotors explorative both cross open tests. Moreover, board study, minimized count head dips observed treated mice. results shown this study demonstrate can be further examined their role adjuvant conventional medications or nutraceuticals.

Language: Английский

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Neuropharmacological and Antidiabetic Potential of Lannea coromandelica (Houtt.) Merr. Leaves Extract: An Experimental Analysis

Evidence-based Complementary and Alternative Medicine, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 10

Published: March 28, 2022

The present study examines the neuropharmacological and antidiabetic properties of methanol leaves extract Lannea coromandelica in animal models. This is carried out by elevated plus-maze apparatus, motor coordination, thiopental sodium has an induction role sleeping time, hole board, cross, open field, studies. Mice were treated doses 100, 150, 200 mg/kg body weight apparatus coordination; 100 field tests; 400 activity test. Extraction specifies a significantly decreased time duration sodium-induced experimental locomotor exploratory behaviors mice open-field hole-cross tests compared to effects control. Furthermore, increased with dose-dependent onset action. hole-board test also demonstrated reduced number head dips. findings showed that L. potential effects. In addition, alloxan-induced diabetic mice, at revealed significant could be used manage blood glucose levels more research.

Language: Английский

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Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

Antioxidants, Journal Year: 2022, Volume and Issue: 11(10), P. 2049 - 2049

Published: Oct. 18, 2022

In the last few decades, endocannabinoids, plant-derived cannabinoids and synthetic have received growing interest as treatment options in neurodegenerative conditions. various experimental settings, they displayed antioxidative, anti-inflammatory, antiapoptotic, immunomodulatory, neuroprotective effects. However, due to numerous targets downstream effectors of their action, cellular molecular mechanisms underlying these effects are rather complex still under discussion. Cannabinoids able neutralize free radicals modulate production reactive oxygen species activity antioxidative systems acting on CB1 CB2 cannabinoid receptors. The activation receptors stimulates signaling pathways involved defense survival (such phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), Nrf2 pathways) regulates glutamatergic signaling, N-methyl-D-aspartate (NMDA) receptors, calcium influx, induction Ca2+-regulated cascades, whereas mediated by suppression microglial release prooxidative proinflammatory mediators. This review summarizes main new advances understanding cannabinoids. Because plethora possible pharmacological interventions related oxidative stress cannabinoid-mediated neuroprotection, future research should be directed towards a better interplay between activated signal transduction with aim improve efficacy targeting endocannabinoid system.

Language: Английский

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The therapeutic potential of purified cannabidiol

Journal of Cannabis Research, Journal Year: 2023, Volume and Issue: 5(1)

Published: June 13, 2023

Abstract The use of cannabidiol (CBD) for therapeutic purposes is receiving considerable attention, with speculation that CBD can be useful in a wide range conditions. Only one product, purified form plant-derived solution (Epidiolex), approved the treatment seizures patients Lennox-Gastaut syndrome, Dravet or tuberous sclerosis complex. Appraisal evidence base complicated by fact products sometimes have additional phytochemicals (like tetrahydrocannabinol (THC)) present, which make identification active pharmaceutical ingredient (API) positive studies difficult. aim present review to critically clinical using only, order establish upcoming indications might beneficial. areas there most support are anxiety (positive data 7 uncontrolled and 17 randomised controlled trials (RCTs)), psychosis schizophrenia 1 study 8 RCTs), PTSD 2 4 RCTs) substance abuse 3 RCTs). Seven improve sleep quality, but this has only been verified small RCT. Limited supports Parkinson’s (3 autism smoking cessation (2 graft-versus-host disease intestinal permeability (1 RCT each). Current does not oral pain (at least as an acute analgesic) COVID symptoms, cancer, Huntington’s type diabetes. In conclusion, published multiple beyond epilepsy. However, limited number investigating effects CBD, testing healthy volunteers, very patient numbers. Large confirmatory phase required all indications.

Language: Английский

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