32 SKIN CARE
160 140 120 100 80 60 40 20 0
Positive control
0.005% 0.05% AnnonaSense CLR
Figure 1: CB2 agonistic effect of the cherimoya active at two different concentrations
show compromised skin health and, indeed coupled to that, a lower level of psychological wellbeing. Skincare products which can act on the compromised immune capacity of skin can improve skin health and wellbeing. How do they do that? To answer this question, a deeper understanding of the skin’s immune functionality is essential.
Zooming into the science Zooming in from irritated skin and sensitive and a lower level of emotional wellbeing to the skin‘s immune capacity, we find that the immune system of the skin consists of subsystems and that there is a hierarchy between these immunological subsystems. Simplified, there is a ‘workforce’ of
subsystems which are busy with their day- to-day jobs of acting on and eliminating stressors, and there is a ‘management’ where a few immunological subsystems regulate physiological health and interact with and direct the ‘workforce’. Obviously, in order to provide an effective
skincare product which improves skin health and wellbeing, the immunological subsystems that act as the ‘management’ are of most interest. Zooming in further, we come to the
recognition of the two main immunological subsystems which act as the ‘management’ of skin health: the endovanilloid and endocannabinoid systems. Interestingly, a clear distinction is present in the roles both subsystems play in skin health. By and large, the endovanilloid system
plays an active role in the loss of skin’s health functionality, inflammation and irritation. The endocannabinoid system, however, acts against the endovanilloid system by directly interfering with it in its effort to regain and maintain health. Again, extrapolating from the above, both immunological sub-systems play a pivotal role in emotional wellbeing. Zooming in even further makes us
understand the most important way of how the PERSONAL CARE June 2023
Placebo■ 3% AnnonaSense CLR■
70 60 50 40 30 20 10 0
250Hz Figure 2: Assessment of skin sensitivity
endocannabinoid system in the skin interacts with the endovanilloid system and, therefore, the ability to regain and maintain skin health. We have now arrived at the cell biological
level and the main cellular receptors, channels and enzymes which play a role in this interaction: CB2 (Cannabinoid Receptor Type 2), AC (Adenylyl Cyclase) and TRPV1 (Transient Receptor Potential Vanilloid 1). TRPV1 is a so-called cation channel with high permeability to calcium. Activation of TRPV1 induces inflammatory processes and irritations.
TRPV1 signaling is infamous for the induction
of itch, burning sensations and pain. It acts through the nerve cells and central nervous system, therefore playing a central role in direct communication between the skin and brain. A real skin-brain connector. TRPV1 can be activated by heat and its specific agonist capsaicin, but also by UV radiation, inflammatory mediators, neuromediators, growth factors and pathogen- produced toxins. The large number of triggers for TRPV1 illustrates its great importance in inflammations and loss of health. Importantly, TRPV1 activation can only take
place when TRPV1 itself is phosphorylated, and this is from which the endocannabinoid system – in this case in the form of CB2 – benefits. For the phosphorylation of TRPV1, protein
kinase A (PKA) is essential. This requires cellular cyclic AMP (cAMP), which is generated by active AC. Hence, for TRPV1 to be a threat to skin
health, active AC is needed. Here lies the most important link between the endocannabinoid and endovanilloid systems. Activation of CB2 leads to the reduction of activity of AC and, therefore, the reduction of the phosphorylation of TRPV1. As a result, TRPV1 is not able, or at least
shows a reduced ability, to induce inflammatory processes, irritation, itch and pain. In other words, by activating CB2, skin health is restored and maintained. Zooming out again, with improved skin
health and reduced TRPV1-induced detrimental signaling, wellbeing is improved and maintained. However biologically complicated the
link between skin health and emotional wellbeing might be, it is feasible to have a true ‘neurocosmetic’ effect when the possibility exists for a cosmetic active ingredient to act as an agonist to CB2 on the outermost skin cells, the keratinocytes. From a consumer perspective, such an
activity will lead to, for instance, less sensitive skin and improvement of wellbeing and quality of life. As touched upon in the first paragraph of this article, such an approach seems to be extremely relevant for today’s consumer. CLR developed AnnonaSense CLR™ (INCI:
Annona Cherimola Fruit Extract) - hereafter known as the cherimoya active - to sustainably achieve skin health and wellbeing by acting on CB2.
In vitro study In a thorough in vitro study, described below, the cherimoya active’s agonistic activity on CB2 was assessed. 293T-CB2 cells which had been stably transfected with cDNA encoding the human cannabinoid receptor 2 (CB2) were incubated in 24 well plates at a density of 1x105 cells/ml and transiently transfected with 0.1 mg/ml of the plasmid CRE-luc containing six consensus cAMP responsive elements (CRE) linked to firefly luciferase. Transient transfection was performed with
Rotifect (Carl Roth GmbH, Karlsruhe, Germany) according to the manufacturer’s instructions. Cells were harvested 24 hours after transfection. To measure the CB2 agonistic activity of ACF,
293T-CB2-CRE-luc cells were treated either with increasing concentrations of the cherimoya active or the positive control WIN-55,212-2 (Sigma Aldrich, Taufkirchen, Germany) for 15 minutes and then with 10 mM Forskolin (Sigma Aldrich, Taufkirchen, Germany). After six hours of stimulation, the cells
were lysed in 25 mM Tris-phosphate pH 7.8, 8 mM MgCl2
, 1 mM DTT, 1% Triton X-100,
www.personalcaremagazine.com 5 Hz
CB2 agonistic activity (%)
Reduction of skin sensitivity (%)
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