Study finds that cannabidiol induces the expression of heme oxygenase 1 in skin cells

At present, cannabidiol has found considerable use not just in the world of cosmetics but also in nutrition and pharmaceutics due to its therapeutic potential and antioxidant properties.

Study finds that cannabidiol induces the expression of heme oxygenase 1 on skin cells
Immunology Professor Eduardo Muñoz. Image Credit: University of Córdoba.

It is a natural molecule derived from medicinal cannabis. Although though it is extracted from cannabis, it is not a psychoactive compound, that is, it has no impact on the nervous system. Despite its successful sales, it is still not known how cannabidiol reacts with various skin cells to release its antioxidants.

A collaboration between the University of Córdoba and the University of Dundee showed, for the first time, that cannabidiol stimulates the expression of heme oxygenase 1, an enzyme with anti-inflammatory and antioxidant properties, in the main cells on the top layer of the skin, known as keratinocytes. This is performed by silencing or reducing the protein that inhibits it, called BACH1.

Once we described the whole working mechanism, we have continued our partnership, making modifications to the cannabidiol molecule in order to try to improve its properties that fight against skin diseases.”

Eduardo Muñoz, Immunology Professor, University of Córdoba

Muñoz is in charge of the BIO-304 “Immunopharmacology and Molecular Virology” research team at the University of Córdoba.

Accordingly, the international research team developed new molecules that not just block the BACH1 protein but also stimulate the NRF2 protein. This protein regulates how specific genes are expressed.

These specific genes enable protecting cells against oxidative stress like HMOX1, the one that encodes heme oxygenase 1, together with several others that work independently of BACH1.

Hence, the newly developed molecules extracted from cannabidiol exhibit double antioxidant activity: firstly, they inhibit BACH1 and thus stimulate the expression of heme oxygenase 1, and secondly, they stimulate NRF2, which also induces the expression of heme oxygenase 1, as well as other antioxidant genes.

When combining the inhibition of BACH1 with the activation of NRF2, the result is a very potent antioxidant and anti-inflammatory response and better therapeutic effects.”

Eduardo Muñoz, Immunology Professor, University of Córdoba

This action mechanism is highly fascinating for skin disease treatments like atopic dermatitis and epidermolysis bullosa—a very rare yet underexplored disease. Also, this molecule exhibits a great capacity for use in cosmetics because of its antioxidant properties.

Apart from the University of Dundee in Scotland and the University of Córdoba, the companies Emerald Health Biotechnology, in the field of developing a new medicine, and Innohealth Madrid (obtained by Evonik Industries AG), which specializes in dermo-cosmetics made from natural elements, also contributed to this research. Both the companies were established by the BIO-304 research team at the University of Córdoba.

In accordance with these studies, the researchers will further modify the molecules to enhance their properties and, subsequently, carry out studies on animal models to interpret its therapeutical potential for skin diseases and other inflammatory diseases.

Source:
Journal reference:

Casares, L., et al. (2020) Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity. Redox Biology. doi.org/10.1016/j.redox.2020.101689.

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