Cannabidiol has a central role in the NF-κB inhibition of a Cannabis sativa L. extract in human keratinocytes

Introduction Cannabis sativa L. contains high concentrations of cannabinoids including cannabidiol (CBD), the second major cannabinoid, devoid of psychotropic activity, and Δ-9-tetrahydrocannabinol (THC). In our previous study, a Cannabis sativa L. ethanolic extract (CSE), standardized in 5% CBD and low concentration of THC, exerted anti-inflammatory effects in keratinocytes, including the downregulation of genes involved in inflammation [1]. CSE and CBD inhibited the nuclear transcription factor κB (NF-κB), but only CSE showed reduction in interleukin-8 (IL-8) secretion.

Aim The aim of the present study was to investigate the contribution of the main constituents of CSE to the biological activities in human keratinocytes.

Method CSE and other purified constituents (cannabinoids, terpenes, and cannflavins) were provided by Linnea SA (Riazzino, Switzerland) and assayed in human keratinocytes (HaCaT) challenged by TNFα.

Results CSE was fractionated into 6 sub-fractions and analyzed for the content of cannabinoids, terpenes, and cannflavins. CBD was the most abundant compound, and the inhibitory activity on NF-κB was related to CBD quantity in the fractions. The evaluation of a reconstituted mixture of purified cannabinoids (proportional to CSE), except for THC, inhibited NF-κB comparably to CSE. Differently, only the reconstituted mixture comprising THC showed inhibition of IL-8.

Conclusion These results suggest that CBD plays a central role in the inhibition of pro-inflammatory mediators in human keratinocytes, acting on the NF-κB pathway. However, other cannabinoids can potentially participate in the inhibition of the IL-8 release, albeit quantitatively lower than CBD, in particular THC.

Publication History

Article published online:
13 June 2022

• References

• 1 Sangiovanni E. et al. Phytother Res 2019; 33: 2083-2093