Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1

Casares, Laura; García, Victor; Garrido‐Rodríguez, Martín; Millán, Estrella; Collado, Juan A.; García‐Martín, Adela; Peñarando, Jon; Calzado, Marco A.; Vega, Laureano de la; Muñóz, Eduardo

doi:10.1016/j.redox.2019.101321

Cited by 133 publications

(135 citation statements)

References 57 publications

(64 reference statements)

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“…The effect of CBD on keratinocytes was examined as follows: all cell groups (control cells, keratinocytes following UVA irradiation, and cells following UVB irradiation) were cultured for 24 h in a medium suplemented with 4 µM CBD (dissolved in ethanol with a final concentration of 0.1%). This concentration of CBD did not alter the morphology or proliferation of keratinocytes [29,30], nor did it affect the cells' viability measured by an MTT assay [28] (data not shown). The control cells were cultured in parallel without treatment.…”

Section: Cell Culture and Treatmentmentioning

confidence: 89%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

101

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Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte differentiation, but oxidative stress also plays an important role in the pathogenesis of this disease. Here, we examined the effect of cannabidiol (CBD), a phytocannabinoid with antioxidant and anti-inflammatory properties, on the redox balance and phospholipid metabolism in UVA/UVB-irradiated keratinocytes isolated from the skin of psoriatic patients or healthy volunteers. CBD accumulates mainly in membrane keratinocytes, especially from patients with psoriasis. This phytocannabinoid reduces the redox imbalance observed in the UV-irradiated keratinocytes of healthy subjects. It does so by decreasing reactive oxygen species (ROS) generation, increasing the Trx-dependent system efficiency, and increasing vitamin A and E levels. Consequently, a reduction in lipid peroxidation products, such as 8-isoprostanes and 4-hydroxynonenal, was also observed. Moreover, CBD modifies redox balance and lipid peroxidation in psoriatic patient keratinocytes following UV-irradiation. Interestingly, these changes are largely in the opposite direction to the case of keratinocytes from healthy subjects. CBD also regulates metabolic changes by modulating the endocannabinoid system that is disturbed by psoriasis development and UV irradiation. We observed a decrease in anandamide level in the UV-irradiated keratinocytes of healthy controls following CBD treatment, while in keratinocytes from patients treated with CBD, anandamide level was increased. However, the level of palmitoylethanolamide (PEA) was decreased in both groups treated with CBD. We further demonstrate that CBD increases CB1 receptor expression, primarily in the keratinocytes of patients, and increases CB2 receptor expression in both the psoriatic and control groups. However, CBD decreases CB2 receptor expression in UV-irradiated keratinocytes taken from patients. The UV- and psoriasis-induced activity of transmembrane transporters (Multidrug-Resistance (MDR) and breast cancer resistance protein (BCRP)) is normalized after CBD treatment. We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.

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Section: Cell Culture and Treatmentmentioning

confidence: 89%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

101

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“…Furthermore, the exact, obviously cell type-dependent mechanism of HO-1 induction by CBD poses a challenge for future investigations. In this context, a recently published study showed that CBD mediates HO-1 expression in keratinocytes Nrf2 independently by inducing the cytosolic proteasomal degradation of the transcriptional repressor BTB and CNC homology 1 (BACH1) and its nuclear export [43]. Accordingly, no inhibition of the CBD-induced HO-1 expression in the presence of Nrf2 siRNA could be registered in the respective work [43].…”

Section: Autophagymentioning

confidence: 99%

Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

Böckmann

Hinz

2020

Cells

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Cannabidiol (CBD), a non-psychoactive cannabinoid, has been reported to mediate antioxidant, anti-inflammatory, and anti-angiogenic effects in endothelial cells. This study investigated the influence of CBD on the expression of heme oxygenase-1 (HO-1) and its functional role in regulating metabolic, autophagic, and apoptotic processes of human umbilical vein endothelial cells (HUVEC). Concentrations up to 10 µM CBD showed a concentration-dependent increase of HO-1 mRNA and protein and an increase of the HO-1-regulating transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). CBD-induced HO-1 expression was not decreased by antagonists of cannabinoid-activated receptors (CB1, CB2, transient receptor potential vanilloid 1), but by the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC). The incubation of HUVEC with 6 µM CBD resulted in increased metabolic activity, while 10 µM CBD caused decreased metabolic activity and an induction of apoptosis, as demonstrated by enhanced caspase-3 cleavage. In addition, CBD triggered a concentration-dependent increase of the autophagy marker LC3A/B-II. Both CBD-induced LC3A/B-II levels and caspase-3 cleavage were reduced by NAC. The inhibition of autophagy by bafilomycin A1 led to apoptosis induction by 6 µM CBD and a further increase of the proapoptotic effect of 10 µM CBD. On the other hand, the inhibition of HO-1 activity with tin protoporphyrin IX (SnPPIX) or knockdown of HO-1 expression by Nrf2 siRNA was associated with a decrease in CBD-mediated autophagy and apoptosis. In summary, our data show for the first time ROS-mediated HO-1 expression in endothelial cells as a mechanism by which CBD mediates protective autophagy, which at higher CBD concentrations, however, can no longer prevent cell death inducing apoptosis.

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“…CBD is a phytocannabinoid present in the resin secreted from trichomes in female C. sativa plants, and is mainly found in inflorescences. The bioactivity of this compound has been related to an enhancement of its antioxidant and neurological activity, among others, by the promotion of several metabolic pathways [4][5][6]. However, the European Union (EU) does not consider CBD supplements as a novel food [7] and lets member states set their own rules over its marketing, leading to a convoluted situation in terms of regulation.…”

Section: Introductionmentioning

confidence: 99%

Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Multi-Residue Analysis of Mycotoxins and Pesticides in Botanical Nutraceuticals

Narváez

Rodríguez-Carrasco

Castaldo

et al. 2020

Toxins

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Cannabidiol (CBD) food supplements made of Cannabis sativa L. extracts have quickly become popular products due to their health-promoting effects. However, potential contaminants, such as mycotoxins and pesticides, can be coextracted during the manufacturing process and placed into the final product. Accordingly, a novel methodology using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was developed to quantify 16 mycotoxins produced by major C. sativa fungi, followed by a post-target screening of 283 pesticides based on a comprehensive spectral library. The validated procedure was applied to ten CBD-based products. Up to six different Fusarium mycotoxins were found in seven samples, the most prevalent being zearalenone (60%) and enniatin B1 (30%), both found at a maximum level of 11.6 ng/g. Co-occurrence was observed in four samples, including one with enniatin B1, enniatin A and enniatin A1. On the other hand, 46 different pesticides were detected after retrospective analysis. Ethoxyquin (50%), piperonyl butoxide (40%), simazine (30%) and cyanazine (30%) were the major residues found. These results highlight the necessity of monitoring contaminants in food supplements in order to ensure a safe consumption, even more considering the increase trend in their use. Furthermore, the developed procedure is proposed as a powerful analytical tool to evaluate the potential mycotoxin profile of these particular products.

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Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1

Cited by 133 publications

References 57 publications

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Multi-Residue Analysis of Mycotoxins and Pesticides in Botanical Nutraceuticals

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