The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress

Ekiner, Sinemyiz Atalay; Gęgotek, Agnieszka; Skrzydlewska, Elżbieta

doi:10.1016/j.redox.2022.102489

Cited by 39 publications

(40 citation statements)

References 139 publications

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“…Cannabidiol (CBD), one of the main compounds in the plant Cannabis sativa, presents a wide range of pharmacological properties, such as anxiolytic, antidepressant, antipsychotic, anticonvulsant and neuroprotective ( Garcia-Gutierrez et al, 2020 ; Kwee et al, 2022 ; Atalay Ekiner et al, 2022 ; Yousaf et al, 2022 ; V Micale et al, 2015 ; Stark et al, 2021 ; Di Bartolomeo et al, 2021 ; Stark et al, 2019 ). These actions have considerably increased the number of studies aimed at clarifying its therapeutic role in various neuropsychiatric diseases, including depressive disorders.…”

Section: Introductionmentioning

confidence: 99%

Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model

et al. 2023

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Introduction: This study aims to further characterize cannabidiol’s pharmacological and molecular profile as an antidepressant.Methods: Effects of cannabidiol (CBD), alone or combined with sertraline (STR), were evaluated in male CD1 mice (n = 48) exposed to an unpredictable chronic mild stress (UCMS) procedure. Once the model was established (4 weeks), mice received CBD (20 mg·kg-1, i.p.), STR (10 mg·kg-1, p.o.) or its combination for 28 days. The efficacy of CBD was evaluated using the light-dark box (LDB), elevated plus maze (EPM), tail suspension (TS), sucrose consumption (SC) and novel object recognition (NOR) tests. Gene expression changes in the serotonin transporter, 5-HT1A and 5-HT2A receptors, BDNF, VGlut1 and PPARdelta, were evaluated in the dorsal raphe, hippocampus (Hipp) and amygdala by real-time PCR. Besides, BDNF, NeuN and caspase-3 immunoreactivity were assessed in the Hipp.Results: CBD exerted anxiolytic and antidepressant-like effects at 4 and 7 days of treatment in the LDB and TS tests, respectively. In contrast, STR required 14 days of treatment to show efficacy. CBD improved cognitive impairment and anhedonia more significantly than STR. CBD plus STR showed a similar effect than CBD in the LBD, TST and EPM. However, a worse outcome was observed in the NOR and SI tests. CBD modulates all molecular disturbances induced by UCMS, whereas STR and the combination could not restore 5-HT1A, BDNF and PPARdelta in the Hipp.Discussion: These results pointed out CBD as a potential new antidepressant with faster action and efficiency than STR. Particular attention should be given to the combination of CBD with current SSRI since it appears to produce a negative impact on treatment.

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Section: Introductionmentioning

confidence: 99%

Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model

et al. 2023

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“…It is believed that these modifications are particularly important for biological activity of Nrf2 transcription factor, because its cytosolic inhibitor—Keap1 is very susceptible to adduct with 4-HNE formation [ 95 ]. However Nrf2 is responsible for the biosynthesis of cytoprotective proteins, including antioxidant proteins, and is also involved in the regulation of the pro-inflammatory pathway at the level of pro-inflammatory cytokines, e.g., TNFα, which promotes the increase in the level of the NFκB transcription factor in keratinocytes and fibroblasts as well as may also enhance intercellular pro-inflammatory signaling [ 59 , 96 , 97 ]. In turn, in fibroblasts, increased oxidative stress favors oxidative modifications of proteins resulting from the formation of carbonyl groups in the protein structure [ 98 ].…”

Section: The Use Of Phytocannabinoids In Counteracting Metabolic Chan...mentioning

confidence: 99%

Phytocannabinoids in the Pharmacotherapy of Psoriasis

Wroński¹,

Jarocka-Karpowicz

Jastrząb

et al. 2023

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Phytocannabinoids are naturally occurring compounds, the main source of which is Cannabis sativa L. Through direct action or interaction with G protein-coupled receptors, they affect ROS and pro-inflammatory cytokines levels and modify the effectiveness of transcription factor responsible for the biosynthesis of antioxidants which lead to oxidative stress and its consequences. Due to the modification of the redox balance and inflammation, phytocannabinoids are used in the treatment of various diseases, including autoimmune dermatoses, such as atopic dermatitis and psoriasis. Psoriasis is one of the most common dermatoses, and one of unknown etiology. A disturbed redox balance with a shift towards the oxidation leads to oxidative stress, resulting in oxidative modifications, mainly of lipids and proteins, and prolonged activation of immune cells and increased generation of pro-inflammatory cytokines, resulting in chronic inflammation. Given the biological activity of phytocannabinoids, they have become the focus of research as components of pharmacotherapy for psoriasis. Beneficial effects were shown by various representatives of phytocannabinoids, but the effect of cannabidiol (CBD) on skin cells (in vitro and ex vivo) and on blood cells from patients with psoriasis vulgaris and psoriatic arthritis has been most often evaluated in recent years.

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“…CBD also has the ability to beneficially regulate the oxidative status in microglia by acting as an antioxidant, where it may directly scavenge ROS and/or inhibit the phosphorylation of upstream kinases needed for NF-κB signaling in primary microglia cells cultured from mice (van den Berg et al, 2001;dos-Santos-Pereira et al, 2020;Atalay Ekiner et al, 2022). This results in reduced levels of IL-1β and TNF-α independently of CB 1 R, CB 2 R or PPARγ, as tested using receptor antagonists.…”

Section: The Impact Of Cannabis On Microgliamentioning

confidence: 99%

Enhancing axonal myelination in seniors: A review exploring the potential impact cannabis has on myelination in the aged brain

Murray

Vecchiarelli

Tremblay

2023

Front. Aging Neurosci.

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Consumption of cannabis is on the rise as public opinion trends toward acceptance and its consequent legalization. Specifically, the senior population is one of the demographics increasing their use of cannabis the fastest, but research aimed at understanding cannabis’ impact on the aged brain is still scarce. Aging is characterized by many brain changes that slowly alter cognitive ability. One process that is greatly impacted during aging is axonal myelination. The slow degradation and loss of myelin (i.e., demyelination) in the brain with age has been shown to associate with cognitive decline and, furthermore, is a common characteristic of numerous neurological diseases experienced in aging. It is currently not known what causes this age-dependent degradation, but it is likely due to numerous confounding factors (i.e., heightened inflammation, reduced blood flow, cellular senescence) that impact the many cells responsible for maintaining overall homeostasis and myelin integrity. Importantly, animal studies using non-human primates and rodents have also revealed demyelination with age, providing a reliable model for researchers to try and understand the cellular mechanisms at play. In rodents, cannabis was recently shown to modulate the myelination process. Furthermore, studies looking at the direct modulatory impact cannabis has on microglia, astrocytes and oligodendrocyte lineage cells hint at potential mechanisms to prevent some of the more damaging activities performed by these cells that contribute to demyelination in aging. However, research focusing on how cannabis impacts myelination in the aged brain is lacking. Therefore, this review will explore the evidence thus far accumulated to show how cannabis impacts myelination and will extrapolate what this knowledge may mean for the aged brain.

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The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress

Cited by 39 publications

References 139 publications

Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model

Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model

Phytocannabinoids in the Pharmacotherapy of Psoriasis

Enhancing axonal myelination in seniors: A review exploring the potential impact cannabis has on myelination in the aged brain

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