90 ANTI-AGEING
function. For example, the horizontal position and fluid redistribution help the wrinkles appear fuller in the morning and not as pronounced.
Folding optimizers BiP is the main chaperone in the ER, involved in the UPR. Additionally, BiP is in charge of guiding the proteins through the folding process.
This chaperone decreases with age,
therefore we wanted to see if the cyclic peptide increases it. To prove that, keratinocytes were treated with the cyclic peptide for 24 hours. Then, cells were lysed, and collecting the lyastes for BiP quantification through ELISA. Total protein content of each sample was
quantified through Micro BCA Protein Assay kit. The peptide showed to significantly increase the BiP chaperone by 24% (p<0.01). Calreticulin in addition to ensure a proper
protein folding, also prevents the aggregation of misfolded proteins. To assess the efficacy of the cyclic peptide
to increase calreticulin, keratinocytes were treated with a solution of the peptide to measure the increase of calreticulin modulation stained by immunofluorescence. Images were acquired using a fluorescence
microscope to determine calreticulin levels, where an increase of 79% in calreticulin was observed (p<0.001) (Figure 1).
Keratinocytes and fibroblast communication Another well-known function of calreticulin is the indirect production of collagen and fibronectin through the synthesis and release of TGβ3. The peptide increases the release of calreticulin by keratinocytes, which in turn induces TGβ3 synthesis in fibroblasts, where collagen is also synthesized. To observe this communication between skin
layers, an in vitro study was conducted where keratinocytes were treated for 48 hours with the cyclic peptide. Then, conditioned medium was collected and transferred to fibroblasts seeded in wells and incubated for four days. Afterwards, they were processed for
immunofluorescence staining against collagen I, resulting in a 136% increase in collagen I (Figure 2) (p<0.01).
De-stressing endoplasmic reticulum Some internal or external factors can alter
NON-STRESSED (CHOP IN VIOLET)
BASAL (CONDITIONED MEDIA IN HDF, COLLAGEN IN GREEN) 0.01 MG/ML CYCLIC PEPTIDE (CONDITIONED MEDIA IN HDF, COLLAGEN IN GREEN)
Figure 2: Fluorescent images of collagen levels in conditioned media from HDF, showing collagen in green, nuclei in blue
our organism. One of the organelles affected by this stress is the ER. In aged skin, this effect produces, as previously mentioned, misfolded proteins, causing them to aggregate, accumulate, and damage the ER, thus generating apoptosis in the cell. To prove the cyclic peptide efficacy under
stress conditions, the following test was performed on three different conditions: one of them subjected to brefeldin A to stress the ER, a second untreated explant, and a third explant treated with the peptide and brefeldin A. CHOP (C/EB homologous protein), a
molecule involved in UPR and a marker of apoptosis, was measured using immunostaining, yielding results of -38% compared to the explant stressed with brefeldin A (p<0.05) (Figure 3).
Organizing skintropy To assess how Poptide organizes skintropy and redefines the wrinkles’ daily cycle, an in vivo study was conducted involving 20 women with slight to moderate wrinkles, aged between 40–60 years old. They applied a cream containing 3% of the
commercial solution of the cyclic peptide on one half of their faces or a placebo on the other half, twice a day for 28 days. Wrinkle depth and volume were measured in crow’s feet using Primos 3D, while skin thickness in the cheeks was measured using ultrasound. Measurements were taken in the morning and in the evening to determine if the peptide is capable not only of reducing wrinkles, but also of balancing the difference between morning and evening wrinkles. Poptide was shown to decrease wrinkles
1% CYCLIC PEPTIDE + ER STRESSED (CHOP IN VIOLET)
both during the day and in the evening. Specifically, after 28 days, it reduces wrinkle depth by 10% in the evening and wrinkle volume by 7% both during the day and in the evening. Additionally, the cyclic peptide, proved to
redefine the wrinkles’ daily cycle by decreasing the gap or fluctuation between morning and evening wrinkles compared to the placebo. Similar results were obtained for skin thickness, where it improved both in the morning and in the evening. In summary, this cyclic peptide showed to
reduce wrinkles but also diminish the difference between morning and evening wrinkles improving the wrinkles' daily cycle.
Conclusion The cyclic peptide showed to organize and assists in the folding of proteins in the ER, opening the door to the cosmetic market to new peptide conformations and structures, as well as new, unexplored targets in the ER. Additionally, it showed to achieve
a reduction in skintropy by increasing chaperones such as BiP and calreticulin, which aid in protein folding and are involved in the UPR. Also, it proved to help prevent apoptosis due to ER stress while significantly increasing collagen synthesis through communication between fibroblasts and keratinocytes. Overall, in volunteers showed to decrease
crow’s feet wrinkles and increase skin thickness in volunteers with aging signs, as well as reducing wrinkle volume and depth, and also improving the WDC by reducing the gap difference between morning and evening wrinkles.
ER STRESSED (CHOP IN VIOLET)
PC
Figure 3: Immunostaining images of CHOP levels on human skin explant of a 42 year-old donor (CHOP in violet) PERSONAL CARE October 2024
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