Emerging potential of cannabidiol in reversing proteinopathies

Dash, Raju; Ali, Md. Chayan; Jahan, Israt; Munni, Yeasmin Akter; Mitra, Sarmistha; Hannan, Md. Abdul; Timalsina, Binod; Oktaviani, Diyah Fatimah; Choi, Hyung Jun; Moon, Il Soo

doi:10.1016/j.arr.2020.101209

Cited by 35 publications

(30 citation statements)

References 241 publications

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“…Moreover, another target for modification by 4-HNE is the ubiquitin-related proteasomal system, wherein the intensive modification combined with the cross-linking of protein molecules may lead to the formation of protein aggregates resistant to degradation and thus inhibit the proteasomal system [ 56 ]. Aggregation may also be promoted by Ca 2+ ion accumulation [ 57 ] and the resulting aggregates may disrupt cellular electrolytic homeostasis and even induce an apoptotic response that may be accompanied by the formation of pores in the membranes [ 57 ]. The results of this work showed a significant increase in the level of 4-HNE adducts with the beta subunit of the proteasome in keratinocyte membranes subjected to UVB and long-term CBD application.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Cannabidiol on the Membrane Proteome of UVB-Irradiated Keratinocytes

Atalay

Gęgotek

2021

Antioxidants

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Ultraviolet (UV) radiation contained in sunlight disturbs the redox state of skin cells, leading to changes in the structures and functions of macromolecules including components of biological membranes. Cannabidiol (CBD), which accumulates in biomembranes, may be a promising protective antioxidant compound. Accordingly, the aim of this study was to compare the effects of short-term (24 h) and long-term (48 h) CBD application on the proteomic profile of biological membranes in UVB-irradiated keratinocytes. The data obtained show that UVB radiation quantitatively and qualitatively modified cell membrane proteins, with a particular research focus on adducts of proteins with the lipid peroxidation products malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE). CBD application reduced the UVB-enhanced level of these protein adducts. This was particularly notable amongst proteins related to cell proliferation and apoptosis. Moreover, CBD dramatically increased the UVB-induced expression of proteins involved in the regulation of protein translation and cell proliferation (S3a/L13a/L7a ribosomal proteins), the inflammatory response (S100/S100-A6 proteins), and maintenance of redox balance (peroxiredoxin-1, carbonyl reductase 1, and aldo-keto reductase family 1 members). In contrast, CBD effects on the level of 4-HNE-protein adducts involved in the antioxidant response and proteasomal degradation process indicate that CBD may protect keratinocytes in connection with protein catabolism processes or pro-apoptotic action.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Cannabidiol on the Membrane Proteome of UVB-Irradiated Keratinocytes

Atalay

Gęgotek

2021

Antioxidants

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“…As a consequence, the level of highly reactive products of polyunsaturated fatty acids oxidative fragmentation such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) as well as the level of their adducts with protein is reduced [ [16] , [17] , [18] ]. Moreover, recent studies indicate that CBD supports the maintenance of proteostasis under oxidative conditions by regulating molecular signalling in the biosynthesis and degradation of proteins under different conditions, in vivo and in vitro [ 17 , 19 , 20 ]. In addition, CBD can modify cell viability by altering the permeability of mitochondrial membranes and calcium metabolism, as well as post-translational modifications and the level of apoptosis regulatory proteins such as Bcl-2 and Bax [ 19 , [21] , [22] , [23] , [24] , [25] ].…”

Section: Introductionmentioning

confidence: 99%

Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network

2021

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Hydrogen peroxide (H 2 O 2 ) is widely used in clinical practice due to its antiseptic properties and its ability to heal wounds. However, due to its involvement in the formation of ROS, H 2 O 2 causes several side effects, including disorders of the metabolism of skin cells and the development of chronic inflammation mediated by oxidative stress. Therefore, this study evaluated the effects of cannabidiol (CBD), a phytocannabinoid known for its antioxidant and anti-inflammatory properties, on the proteome of keratinocyte membranes exposed to H 2 O 2 . Overall, the hydrogen peroxide caused the levels of several proteins to increase, while the treatment with CBD prevented these changes. Analysis of the protein-protein interaction network showed that the significant changes mainly involved proteins with important roles in the proteasomal activity, protein folding processes (regulatory subunit of the proteasome 26S 6A, beta proteasome subunit type 1, chaperonin 60 kDa), protein biosynthesis (40S ribosomal proteins S16, S2 and ubiquitin-S27a), regulation of the redox balance (carbonyl reductase [NADPH] 1 and NAD(P)H [quinone] 1 dehydrogenase) and cell survival (14-3-3 theta protein). Additionally, CBD reduced the total amount of MDA, 4-HNE and 4-ONE-protein adducts. Therefore, we conclude that CBD partially prevents the changes induced by hydrogen peroxide by reducing oxidative stress and maintaining proteostasis networks. Moreover, our results indicate that combination therapy with CBD may bring a promising approach in the clinical use of hydrogen peroxide by preventing its pro-oxidative and pro-inflammatory effect through potential participation of CBD in membrane mediated molecular signaling.

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“…Alzheimer’s disease (AD), the most prevalent age-associated neurodegenerative disorder with cognitive decline, is characterized by the presence of intracellular neurofibrillary tangles, consisting of hyperphosphorylated tau protein, and extracellular senile plaques composed of amyloid-beta (Aβ) peptide [ 80 ]. These two major pathological hallmarks contribute to changes in numerous cellular and subcellular events, such as mitochondrial dysfunction, redox imbalance, and neuroinflammation that lead to activation of neurotoxic cascade towards cell death, thereby impairing synaptic communication [ 81 , 82 ].…”

Section: Benefits Of Black Cumin On Human Health and Disease Conditionsmentioning

confidence: 99%

Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety

et al. 2021

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Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb–drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.

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Emerging potential of cannabidiol in reversing proteinopathies

Cited by 35 publications

References 241 publications

Protective Effects of Cannabidiol on the Membrane Proteome of UVB-Irradiated Keratinocytes

Protective Effects of Cannabidiol on the Membrane Proteome of UVB-Irradiated Keratinocytes

Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network

Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety

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