MARINE INGREDIENTS 45 n CyWhite After 4 weeks
10% 9% 8% 7% 6% 5% 4% 3% 2% 1% 0%
After 8 weeks
Figure 5: Effect of CyWhite on ITA° of pigmentation spots of the face after 8 weeks of application compared to the placebo.
antagonist. It blocks α-MSH from bonding with its MC1-R receptor, thereby preventing activation. This is how the Agouti protein inhibits the reaction cascade that would result in tyrosinase activation.11
Lastly, DKK1
(dickkopf WNT signalling pathway inhibitor 1) is a gene expressed in fibroblasts that codes for a protein inhibiting melanocyte proliferation and differentiation as well as melanin pigment production by modulating MITF, a primary tyrosinase expression regulator.12
This is the substance that causes pale colouring in palmoplantar areas.7
Genes involved in skin pigmentation regulation: ideal targets Reconstituted human epidermis models were analysed in a study of the effects of CyWhite (now referred to as ‘the Rainbow wrack lightener’) (product tested at 1% in a cream base) on the expression of pigmentation regulating genes. Either a product that contained the Rainbow wrack lightener or one not containing this agent was applied topically on the reconstituted epidermis models. These products were applied 6 times over 16 days. At the end of the 16th day, gene expression was analysed using full transcriptomics.13 The study results show that
melanogenesis activation was inhibited in keratinocytes with the Rainbow wrack lightener. A comparative analysis between the control sample and treatment showed a 46% reduction in POMC gene expression with the Rainbow wrack lightener. That reduction decreases the synthesis of molecules involved in α-MSH protein expression (Fig 3). Melanogenesis activation
June 2020 0
-1 -2 -3 -4 -5 -6 -7 -8 -9
-10 -11 -12 -13 -14 -15
n CyWhite After 8 weeks
-4.8%
-12.1%***
***p<0.001 test de Student
Figure 6: Effect of CyWhite on the colour difference ΔE between a pigmentation spot and the “normal” skin of the face.
was likewise regulated by the increase in synthesis of the competitor molecule for α- MSH, also known ASP protein, a product of the AGRP gene. Thus, when the active treatment was applied, ASP protein synthesis pathways were stimulated and competed for α-MSH bonding with melanocyte receptors. AGRP gene expression variation increased by 117% compared to the non-activated control product. This also impeded melanogenesis activation (Fig 4). Melanogenesis was also inhibited in melanocytes when the Rainbow wrack lightener was present. DKK1 expression increased by 48% in comparison with the study control, thereby promoting tyrosinase expression inhibition through MITF. DKK1 negatively affected proliferation and melanocyte differentiation pathways and caused a decrease in melanin synthesis (Fig 4). During the last skin pigmentation phases
(melanosome transfer and degradation in keratinocytes), the the Rainbow wrack lightener composite naturally balanced melanin quantities in a variety of ways. On the one hand, the Rainbow wrack lightener reduced SCTE gene expression by 37%, meaning that it had a negative effect on melanosome transfer to keratinocytes, and thus on skin pigmentation (Fig 3). On the other hand, the product increased CTSL2 expression by 35%, and therefore exerted an effect on melanosome and melanin degradation in keratinocytes, reducing the degree of skin pigmentation (Fig 4).
In vivo efficacy: overall assessment of homogeneity and lightening effect The the Rainbow wrack lightener study (test
of the product at 1% in a cream base or placebo cream with no active ingredient) was performed on 2 panels of 23 volunteers each who applied the product twice per day. Efficacy was assessed using colorimetric analysis via cross-polarised numeric photography. This method measures two parameters: individual typology angle (ITA°) and colour deviation (ΔE*). Image acquisition analysis was carried out on 3/4 of the face in reproducible lightening conditions. Follow-up consisted of observing changes in skin pigmentation. In terms of ITA, the greater the angle, the lighter the skin tone. An increase in ITA between T0 and Tn therefore indicates a whitening effect. ΔE* highlights the colour difference between two areas of skin and helps to determine skin tone homogeneity. In both cases, a negative value denotes a reduction in colour contrast between dark blemishes and normal skin. All study data were collected through a randomised, double-blind trial focusing on the nature of the two products tested (cream with the active ingredient and a placebo cream with no active ingredient). Distribution normality was verified using the Shapiro-Wilk test. Statistical analysis of changes in the parameters measured during the study was carried out using the Student or Wilcoxon tests. In this study, the individual typology
angle of facial blemishes increased when the Rainbow wrack lightener was present. Results demonstrated a 7% increase in ITA after 8 weeks compared to the placebo (Fig 5). This result means that pigmented blemishes were lightened. Moreover, ΔE
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Variation of ITA compared to placebo
Colour difference ∆E* compared to placebo (%)
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