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ANTI-AGEING


Cannabinoids for the prevention of ageing


Alexia Blake, Head of Product Development & Product Research – Cellular Goods


The anti-ageing products market is projected to reach $47.8 billion by 2027. Until now, this burgeoning segment has been dominated by active ingredients like ascorbic acid (vitamin C), retinoids, and α- and β-hydroxy acids. Yet despite their proven efficacy for


addressing signs of ageing skin, these ingredients are notorious for causing irritation and photosensitivity, particularly in the case of retinoids and exfoliating acids. For the 50-60% of men and 60-70% of women who report some degree of sensitive skin, these side-effects can hinder long-term use of these ingredients and, in the short-term, lead to a frustrating trial- and-error experiment. Herein lies the exciting promise of


cannabinoids as active skincare ingredients. Generally speaking, the vast majority of research conducted to date has focused on cannabidiol (CBD) and δ9-tetrahydrocannabinol (THC), as these are the most abundant and readily available cannabinoids produced by the plant species Cannabis Sativa L. However, the recent adoption of well- established manufacturing methods, namely biosynthesis and chemical synthesis, have facilitated the commercial availability of other cannabinoids, ushering in a new era of cannabinoid R&D while creating a reliable supply chain defined by high-purity, consistent, sustainable and compliant ingredients. Cannabigerol (CBG) and cannabidiol (CBD) in particular have been shown to counteract the inflammatory effects of exposure to UVA and UVB light, bacterial pathogens and chemical irritants. They also possess superior antioxidant capacity to vitamin C and the ability to inhibit lipid peroxidation caused by UVB exposure. These combined properties open the door


to an entirely new range of active skincare treatments that do not pose risks of irritation and photosensitivity. Cellular Goods has carried out extensive research on them.


UVB-induced lipid peroxidation Lipid peroxidation is a well-established outcome of UV exposure that is linked to extra-cellular matrix (ECM) breakdown and premature signs of photoageing. For this reason, the ability of CBG and CBD to inhibit lipid peroxidation alone and in combination was evaluated in a study involving EpiDerm 3D cultured human epidermal skin tissues, pre-treated with test materials. 4-Hydroxynonenal (4-HNE) formation as an indicator of lipid peroxidation was measured


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12 10 8 6 4 2 0


<0% 27% 48%


100% **


>100% **


90% *


54%


74% *


63% *


90% *


85% *


79


+ UVB (200mJ/cm2


) Figure 1: 4-HNE levels in tissue lysates after UVB irradiation (200mJ/cm2 ) & material treatments


in EpiDerm. Note: Data represent average ± SEM cumulative data from n=3 tissues per group. Significance compared to +UVB control group (** p ≤ 0.01, * p ≤ 0.05). Data labels represent mean % inhibition relative to +UVB control group


from tissue lysates following exposure to UVB radiation (200 mJ/cm2


, 280-340nm). Ascorbic


acid was used as a positive control for lipid peroxidation. The results measured by 4-HNE showed that


UVB radiation exposure significantly increased lipid peroxidation in epidermal tissue (Figure 1). CBD (0.5%), CBG (0.75%, 1%) and combinations (0.25% CBD + 0.25% CBG, 0.375% CBD + 0.375% CBG) provided statistically significant inhibition of lipid peroxidation compared to the UVB- exposed vehicle control. Additionally, 0.5% CBD was more effective than CBG. Specifically, there was a dose- dependent increase in activity for CBG, meaning that higher doses resulted in less lipid peroxidation, whereas CBD had a dose- dependent decrease in activity whereby lipid peroxidation increased with CBD concentration. The combination of CBD and CBG produced


a similar effect to CBD treatments, with a dose-dependent decrease in inhibition activity observed. Based on this data, it was concluded that both CBD and CBG protected against significant UVB-induced lipid peroxidation in 3D skin tissue models. Furthermore, the differentiated dose-response suggests that less


may sometimes be more, which is an important consideration in the context of cannabinoid product development. UVB exposure is known to cause sunburns, which is associated with an inflammatory response within the skin that involves the release of a range of inflammatory cytokines, including Interleukin 8 (IL-8).1,2


IL-8 has also


been linked to inflammageing of skin, making this another highly relevant target in the context of ageing prevention.3-5 Therefore, the anti-inflammatory activity


of CBG, CBD and select combinations of both cannabinoids was evaluated in a similar study with pre-treated, 3D cultured human epidermal skin tissues, whereby IL-8 formation was quantified using enzyme-linked immunosorbent assay (ELISA) 24 hours post-UVB irradiation and incubation with test materials. Clobestasol propionate was used as a


positive control for anti-inflammatory activity. UVB irradiation (200 mJ/cm2


, 280-340 nm)


produced a significant increase in IL-8 release in culture media suggesting a pro-inflammatory response by UVB (Figure 2). Clobetasol propionate showed a complete decrease (100%) in IL-8. All cannabinoid


June 2022 PERSONAL CARE


Untreated + Vehicle UVB+Vehicle UVB+Ascorbic Acid (1.7%) UVB+CBD (0.5%) UVB+CBD (0.75%) UVB+CBD (1%) UVB+CBD (0.5%) UVB+CBD (0.75%)


UVB+CBD (0.25%) + CBG (0.25%) UVB+CBD (1%)


UVB+CBD (0.375%) + CBG (0.375%) UVB+CBD (0.5%) + CBG (0.5%)


4-HNE (µg)/total protein (µg)


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