The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress

Abstract

Cannabidiol (CBD), the major non-psychoactive phytocannabinoid of Cannabis sativa L., is one of the most studied compounds in pharmacotherapeutic approaches to treat oxidative stress-related diseases such as cardiovascular, metabolic, neurodegenerative, and neoplastic diseases. The literature data to date indicate the possibility of both antioxidant and pro-oxidative effects of CBD. Thus, the mechanism of action of this natural compound in the regulation of nuclear factor 2 associated with erythroid 2 (Nrf2), which plays the role of the main cytoprotective regulator of redox balance and inflammation under oxidative stress conditions, seems to be particularly important. Moreover, Nrf2 is strongly correlated with the cellular neoplastic profile and malignancy, which in turn is critical in determining the cellular response induced by CBD under pathophysiological conditions. This paper summarizes the CBD-mediated pathways of regulation of the Nrf2 system by altering the expression and modification of both proteins directly involved in Nrf2 transcriptional activity and proteins involved in the relationship between Nrf2 and the nuclear factor kappa B (NF-κB) which is another redox-sensitive transcription factor.

Graphical abstract

Highlights

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  CBD presents a multi-directional redox modulatory activity with both antioxidant and pro-oxidant effects.

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  CBD promotes changes in a broad spectrum of Nrf2 biological activity across in a concentration-dependent manner.

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  CBD modulates the redox status and inflammation of cells and associated cellular response to oxidative stress via participation in the Nrf2 - NF-κB crosstalk.