Dermatitis and psoriasis are inflammatory diseases in which keratinocytes, the most abundant cells in the epidermis, play a key role in the release of numerous pro-inflammatory mediators (e.g. IL-8, MMP9, and VEGF) [1,2]. IL-8 is involved in neutrophil recruitment and VEGF regulates the angiogenesis process, while MMP9 contributes to extracellular matrix degradation. These pro-inflammatory mediators are regulated by different transcription factors, including NF-κB. Cannabidiol (CBD) [3] is the second major cannabinoid occurring in Cannabis sativa L. (C. sativa) and its anti-inflammatory activity on skin has been demonstrated in mice [4]; however, no studies on human keratinocytes inflammation have been reported so far.
The aim of this work was to evaluate the anti-inflammatory activity of two C. sativa extracts, standardized in CBD and cannabidiolic acid (CBDA), in human keratinocytes. The extracts, containing 1% or 5% CBD+CBDA, were prepared by LINNEA SA (Riazzino, Switzerland). IL-8, MMP-9 and VEGF release were analyzed by ELISA assays, NF-κB driven transcription by a reporter plasmid, while gene expression by real-time PCR.
Both the extracts inhibited IL-8, MMP9 and VEGF release and NF-κB driven transcription induced by TNFα, with IC50s below 50 μg/mL, while CBD was active only on NF-κB driven transcription (IC50: 2.85 μM), suggesting that other compounds are involved in the biological activity.
The extract containing 5% CBD+CBDA (25 μg/mL) and the corresponding concentration of cannabidiol (4 μM) were tested on the expression of 84 genes related to inflammation. The extract decreased the mRNA levels of several pro-inflammatory genes and for some of them CBD was responsible, at least in part, for the activity.
These results suggest that C. sativa extracts may counteract the cutaneous inflammatory processes.
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[2] Majtan J. Arch Dermatol Res 2013.
[3] Burstein, S. Bioorg Med Chem 2015.
[4] Lodzki M. J Control Release 2003.
