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SKIN MICROBIOME 45


commensal microbiota, this synergic cocktail can stimulate the synthesis of wellbeing related neurochemicals (oxytocin) through an in situ produced postbiotic.


T0d


In vitro efficacy Several in vitro tests were performed to demonstrate the modulation of the skin microbiota in situ postbiotic thanks to the active.


In vitro 1: Characterization of the bacterial in situ postbiotic To better understand the mechanism of action of the microbial in situ postbiotic, screening analyses have been performed on the bacterial SuperNatant (bSN). The composition of those bSN was evaluated with the aim to link this specific metabolic profile with this activation of ‘pleasure’ neurochemicals. Compared to placebo, the results of the


postbiotic generated after the application of Kannabia SensePLF


were statistically significant


by achieving the modulation of microbial stress and virulence related metabolites. Thanks to these positive environmental conditions, the consequently secreted in situ postbiotic will be full of balanced healthy and beneficial molecules for our skin.


In vitro 2: Analysis of the microbiota-skin brain axis networks A series of sophisticated and originally designed studies were performed in order to evaluate the active’s ability to activate directly and/or indirectly the neurochemical networks for ‘feeling good’ through the microbiota skin- brain axis. In the 6 steps of this cell-to-cell


communication chain (active ingredient, microbiota, keratinocytes, sensory neurons), the effect of the active was compared with that of the supernatant/s in order to analyze the direct effect at the same time as the indirect activity: The oxytocin levels were analyzed in both


keratinocytes and sensory neurons after applying the active: l Oxytocin levels in Keratinocytes (NHEK- Step 4): The active increased the oxytocin


D0 (15 min) KANNABIA SENSE PLF


Inferior Temporal Gyrus Anterior Cingulate Cortex Pallidum Cerebellum Frontal orbital Cortex Vermis


synthesis on NHEK by up to 1.5-fold versus untreated control and the bacterial supernatant (bSN) increased even more the oxytocin synthesis on NHEK, by up to 3- fold versus control (Fig 1). The active directly activates the oxytocin


production in keratinocytes, but its effects were higher by activating it indirectly through skin microbiome stimulation. The bSN indirect effect was significantly higher than the direct effect of the active: l Oxytocin levels in sensory neurons (Step 6): The active increased the oxytocin synthesis


on sensory neurons by up to 9-fold versus untreated control. The keratinocytes’ supernatant also increased the oxytocin synthesis on sensory neurons NHEK, by up to 8-fold versus control (Fig 2). Therefore, the active directly activates the


oxytocin production in sensory neurons, and indirectly through skin microbiota mediated keratinocyte stimulation. The active centers its mechanism of action


in activating the cascade of reactions from the skin microbiota to the brain, even having a direct effect.


D28


Superior Temporal Gyrus Middle Temporal Gyrus Anterior Insula Amygdala Subcallosal Cortex Vermis


In vivo efficacy The clinical evaluation was a solid scientific argument to demonstrate the efficacy of the active on several clinical trials performed.


In vivo 1: Evaluation of skin well-aging effect The first in vivo test was performed on a 40- volunteer panel aged between 46 and 64 years old. The study was a double blind intra-individual vs placebo, with 2 daily applications for 28 days. l Mood wrinkles (marionette & frown lines): The anti-wrinkle effect of the active was


evaluated on a subgroup of 30 volunteers by Bio3D Structured-light Scanner, a refined 3D digitizing system developed by Bionos Biotech, S.L. This unique software is based on structured light projection which uses 290 pictures per second to prevent movement effects and allow very high- resolution images. The measured parameters were area


and length of the so-called emotional wrinkles after 28 days of treatment (Fig 3). The results showed a reduction of up to


44% and 28% in both area and length of the wrinkles in marionette lines and up to 27% and 32% of both area and length of wrinkles in frown lines at 1% dosage. l Skin hydration Compared to placebo, the application of


Placebo


Frontal Gyrus Cerebellum Insular Cortex Hippocampus


Temoral Fusiform Cortex Default Mode LP


a cream containing 1% dosage of the active increased the skin hydration levels of the 40 volunteers at 8% more than at the beginning of the study and by 1.7-fold at 28 days of treatment. l Skin radiance Finally, there was another 30-volunteer


Figure 4: Clinical evaluation of the brain activation by fMRI. October 2020


group who applied a cream containing 2% active, being demonstrated that their skin gloss and radiance increased by 1.2-fold


PERSONAL CARE NORTH AMERICA T28d ROI (mm2Area )


Length (mm)


Before After Vol.#6


Frown


Marionette lines


Figure 3: Clinical evaluation of wrinkles.


Activated zones


Activated zones


Activated zones


Activated zones


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