Department of Biochemistry, CHA University School of Medicine, Seongnam, Korea.
COSMAX BTI R&I Center, Seongnam, Korea.
J Dermatol Sci. 2023 Feb;109(2):61-70. doi: 10.1016/j.jdermsci.2023.01.008. Epub 2023 Jan 24.
Cannabidiol, a non-psychoactive phytocannabinoid, has antioxidant and anti-inflammatory activity in keratinocytes. However, the signaling pathway through which cannabidiol exerts its effect on keratinocytes or whether it can modulate keratinocyte differentiation has not been fully elucidated yet.
We investigated whether cannabidiol modulates epidermal differentiation and scavenges reactive oxygen species through the aryl hydrocarbon receptor (AhR) in keratinocytes and epidermal equivalents.
We investigated the cannabidiol-induced activation of AhR using AhR luciferase reporter assay, qRT-PCR, western blot, and immunofluorescence assays. We also analyzed whether keratinocyte differentiation and antioxidant activity are regulated by cannabidiol-induced AhR activation.
In both keratinocytes and epidermal equivalents, cannabidiol increased both the mRNA and protein expression of filaggrin, involucrin, NRF2, and NQO1 and the mRNA expression of the AhR target genes, including CYP1A1 and aryl hydrocarbon receptor repressor. Additionally, cannabidiol showed antioxidant activity that was attenuated by AhR knockdown or co-administration with an AhR antagonist. Moreover, cannabidiol increased the ratio of OVOL1/OVOL2 mRNA expression, which is a downstream regulator of AhR that mediates epidermal differentiation. In addition to increased expression of barrier-related proteins, cannabidiol-treated epidermal equivalent showed a more prominent granular layer than the control epidermis. The increased granular layer by cannabidiol was suppressed by the AhR antagonist.
Cannabidiol can be a modulator of the AhR-OVOL1-filaggrin axis and AhR-NRF2-NQO1 signaling, thus indicating a potential use of cannabidiol in skin barrier enhancement and reducing oxidative stress.
大麻二酚是一种非精神活性植物大麻素，具有角质形成细胞的抗氧化和抗炎活性。然而，大麻二酚作用于角质形成细胞的信号通路，或其是否能调节角质形成细胞分化，尚未完全阐明。
我们研究了大麻二酚是否通过角质形成细胞和表皮等效物中的芳香烃受体（AhR）调节表皮分化和清除活性氧。
我们使用 AhR 荧光素酶报告基因检测、qRT-PCR、western blot 和免疫荧光检测来研究大麻二酚诱导的 AhR 激活。我们还分析了角质形成细胞分化和抗氧化活性是否受大麻二酚诱导的 AhR 激活调节。
在角质形成细胞和表皮等效物中，大麻二酚均增加了丝聚蛋白、兜甲蛋白、NRF2 和 NQO1 的 mRNA 和蛋白表达，以及 AhR 靶基因 CYP1A1 和芳香烃受体抑制剂的 mRNA 表达。此外，大麻二酚表现出抗氧化活性，这种活性可被 AhR 敲低或与 AhR 拮抗剂共同给药所减弱。此外，大麻二酚增加了 OVOL1/OVOL2 mRNA 表达的比例，这是一个介导表皮分化的 AhR 下游调节因子。除了增加屏障相关蛋白的表达外，大麻二酚处理的表皮等效物比对照表皮显示出更明显的颗粒层。大麻二酚增加的颗粒层被 AhR 拮抗剂所抑制。
大麻二酚可以作为 AhR-OVOL1-丝聚蛋白轴和 AhR-NRF2-NQO1 信号的调节剂，因此表明大麻二酚在增强皮肤屏障和减少氧化应激方面有潜在的用途。
