Exploring new ways to regenerate the barrier function of the skin
While Cannabidiol is widely known for its soothing properties, the transcriptomic study of Optima CBD revealed the importance of a broader dimension of its properties. We discovered that, in fact, the majority of biological networks activated by CBD are involved in the processes of epidermal differentiation, the formation of the cornified envelope and the maintenance of its integrity. These results lead us to reassess the benefits of CBD and, at the same time, to rethink its immuno-inflammatory activity in relation to the physical dimension of the barrier function.
The barrier function is traditionally associated with the stratum corneum. As the outermost layer of the epidermis, the stratum corneum’s low permeability makes it a genuine physical barrier against external aggression. It protects the skin from temperature variations, dehydration and solar radiation, prevents the penetration of chemical compounds, pollutants or pathogenic microorganisms, and thus limits harmful interactions with the deeper layers of the skin.
The functional quality of this mechanical barrier obviously depends on the integrity of its structure, composed essentially of corneocytes. Their formation occurs in the final phase of the keratinocyte differentiation process. For this to occur, cell proliferation must stop. The renewal of the barrier function can thus be understood as a balance of cyclical processes. It is precisely on these processes that CBD appears to act.
Optima CBD helps regenerate the stratum corneum
The study conducted by Spectrums Europe in partnership with Eurofins was carried out on skin explants, with 0.1% Optima CBD treatment on D2, D5 and D7, and RNA extraction on D5 and D8. The observations detailed here are those made on D8. They reveal that Optima CBD significantly regulates several genes belonging to the EDC (epidermal differentiation complex) locus, involved in the keratinocyte differentiation process, suggesting an improvement in the formation of corneocytes, the structure of the stratum corneum and hence the barrier function.
At the same time, we noted the activation of EVPLL (Envoplakin like), a gene relatively unnoticed in cosmetics, yet associated with desmosomes and the cornified enveloppe. We also observed the stimulation of the expression of several genes from the LCE (Late Cornified Envelope) family. These genes are particularly interesting because the associated proteins are the last to be synthesized, during the terminal phase of differentiation. They complete the cornification process and are involved in several related processes.
Still in the EDC (Epidermal Differentiation Complex) family, Optima CBD XB stimulates the expression of FGL2 (filagrin 2) and CTSH (cathepsin H) genes, closely correlated with filaggrin production. Filaggrin and filaggrin-2 are two proteins strongly involved in the quality of the differentiation process, particularly at the cornification stage. They are then broken down into the amino acids that make up NMF (natural moisturizing factor), which helps seal the skin barrier. A deficiency of these two proteins results in more permeable skin, leading to atopic dermatitis.
Finally, Optima CBD increases the expression of AQP9, which ensures the impermeability of the barrier and plays a role in its repair.
While the study indicated an action on the formation and quality of the stratum corneum, it also enabled us to understand the kinetics of the molecule in the epidermal regeneration cycle.
Optima CBD kinetics, between growth arrest and activation of cell differentiation
Remarkably, OPTIMA CBD modulates a number of genes associated with keratinocyte proliferation arrest. Starting with increased the expression of TRPV1. While activation of this receptor is frequently linked to anti-inflammatory processes, its expression is also associated with the arrest of keratinocyte proliferation. In parallel, we observed the inhibition of genes whose expression is associated with keratinocyte proliferation – AREG (Amphiregulin), EPHA2 (EPH Receptor A2), or ODC1 (ornithine decarboxylase).
Optima CBD also activate the BCL11B (BCL11 Transcription Factor B), which is particularly crucial to epidermal homeostasis and barrier function.
Optima CBD also activates numerous genes involved in cell differentiation: S100B, HES1, KRT1, DEFB4A or MAF and MAFB, which lead to terminal differentiation. Other interesting pathways: LFNG associated with the activation of the Notch pathway, which is known to lead to the activation of differentiation, and FASN, involved in both differentiation and fatty acid formation.
This points to the hypothesis of an active ingredient acting at the pivotal moment between the arrest of the proliferation process and the onset of differentiation. This hypothesis is confirmed by the activation of characteristic genes, P2RY1 and P2RY2 (Purinergic Receptor P2Y1 and P2RY2).
A sensitive skin active, Optima CBD’s primary role would be to regulate keratinocyte proliferation and support the various pathways involved in the formation of the stratum corneum. In the next articles of this series, we’ll see how its properties relate to the other dimensions of the barrier function.