The anti-acne and anti-ageing activity of a new hexapeptide in complex with zinc and its comparison to retinol
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Presented by: Iva Dolečková
Introduction:
Materials and methods:
The hexapeptide was prepared by the standard solid phase peptide synthesis and zinc sulfate was used for the preparation of the Zn-peptide complex. HaCaT keratinocytes were treated with the corresponding concentrations of Zn-peptide; hexapeptide and zinc sulfate; and 10 µM retinol. For induction of the pro-inflammatory interleukins, the cells were irradiated with UVB before the treatments. The gene expression of 5α-reductase, type I (SRD5A1), proteins involved in epidermal keratinization (FLG, OCLN, LCE2C, SPRRE2, KRT10) and the interleukins IL1α, IL6 and IL8 was determined by quantitative, real-time RT-PCR (qRT-PCR). The antimicrobial activity was determined by OD590 measurement of C. acnes suspension culture treated with the corresponding concentrations of Zn-peptide, hexapeptide and zinc sulfate. We also performed a double-blind, placebo-controlled, split-face in vivo study on Caucasian volunteers with acne-prone skin. 30 volunteers (27 women/3 men, 18-48 years) applied emulsion with 13.5 µg/mL Zn-peptide and placebo emulsion; and 10 volunteers (9 women/1 man, 24-49 years) applied emulsion with 0.2 % retinol and placebo emulsion once daily in the evening for 6 weeks. The number of inflammatory acne lesions, number of skin pores, skin redness and the amount of protoporphyrin IX was determined by an image analysis of whole-face pictures obtained by a VisiaCR camera. Sebum was determined by a sebumeter, transepidermal water loss (TEWL) by a tewameter, wrinkle depth by a Primos 3D camera, elasticity by a cutometer and collagen level by reflectance confocal microscopy (Vivascope 3000).
Results and discussion:
Zn-peptide downregulated 5α-reductase gene expression, a key enzyme involved in androgens-driven hyperseborrhoea, suppressed expression of IL1α inducing epidermal hyperkeratinization and lowered the selected keratinization markers. Its anti-inflammatory properties were demonstrated by the inhibition of the pro-inflammatory interleukins. Finally, the antimicrobial activity towards C. acnes was confirmed. The in vitro effects of Zn-peptide were better than that of the hexapeptide alone, zinc sulfate alone or 10 µM retinol. In vivo study showed that Zn-peptide significantly reduced the number of the inflammatory lesions, number of skin pores, it also decreased skin redness, sebum level and the amount of protoporphyrin IX corresponding to the C. acnes number. We also observed its anti-ageing effect represented by wrinkle reduction, elasticity improvement and collagen increase. Both the anti-acne and anti-ageing effects of Zn-peptide were better than that of 0.2 % retinol. Moreover, retinol gradually increased TEWL suggesting skin barrier disruption which might contribute to the irritation commonly observed after retinoids application. On the other hand, significantly reduced TEWL values were found after Zn-peptide treatment.
Conclusion:
Zn-peptide proved to be a new, multifunctional compound targeting all key processes involved in acne pathogenesis. It significantly improved appearance of the acne-prone skin and also showed an anti-ageing effect. Its biological activity was better than that of its individual components or retinol. Importantly, Zn-peptide did not show any irritation potential in comparison to retinol.
Acne vulgaris is a common chronic skin disease affecting individuals of all ages. The pathogenesis of acne is characterized by four core events: hyperseborrhoea, epithelial hyperkeratinization, Cutibacterium acnes colonization and inflammation. Due to the multifactorial nature of the disease, a combination therapy or use of multifunctional compounds are the preferred approaches. Retinoids are among the most effective compounds targeting multiple acne-associated pathways. However, they often cause negative adverse effects including skin dryness and irritation. Therefore, there is still a need for new, more effective and safer alternatives. In this study, we evaluated a new hexapeptide in complex with zinc (Zn-peptide) for its ability to inhibit the key acne-related processes in vitro and to improve the appearance of the acne-prone skin in vivo. The effects were compared to its individual components and retinol as a representative retinoid commonly used in cosmetics.
Materials and methods:
The hexapeptide was prepared by the standard solid phase peptide synthesis and zinc sulfate was used for the preparation of the Zn-peptide complex. HaCaT keratinocytes were treated with the corresponding concentrations of Zn-peptide; hexapeptide and zinc sulfate; and 10 µM retinol. For induction of the pro-inflammatory interleukins, the cells were irradiated with UVB before the treatments. The gene expression of 5α-reductase, type I (SRD5A1), proteins involved in epidermal keratinization (FLG, OCLN, LCE2C, SPRRE2, KRT10) and the interleukins IL1α, IL6 and IL8 was determined by quantitative, real-time RT-PCR (qRT-PCR). The antimicrobial activity was determined by OD590 measurement of C. acnes suspension culture treated with the corresponding concentrations of Zn-peptide, hexapeptide and zinc sulfate. We also performed a double-blind, placebo-controlled, split-face in vivo study on Caucasian volunteers with acne-prone skin. 30 volunteers (27 women/3 men, 18-48 years) applied emulsion with 13.5 µg/mL Zn-peptide and placebo emulsion; and 10 volunteers (9 women/1 man, 24-49 years) applied emulsion with 0.2 % retinol and placebo emulsion once daily in the evening for 6 weeks. The number of inflammatory acne lesions, number of skin pores, skin redness and the amount of protoporphyrin IX was determined by an image analysis of whole-face pictures obtained by a VisiaCR camera. Sebum was determined by a sebumeter, transepidermal water loss (TEWL) by a tewameter, wrinkle depth by a Primos 3D camera, elasticity by a cutometer and collagen level by reflectance confocal microscopy (Vivascope 3000).
Results and discussion:
Zn-peptide downregulated 5α-reductase gene expression, a key enzyme involved in androgens-driven hyperseborrhoea, suppressed expression of IL1α inducing epidermal hyperkeratinization and lowered the selected keratinization markers. Its anti-inflammatory properties were demonstrated by the inhibition of the pro-inflammatory interleukins. Finally, the antimicrobial activity towards C. acnes was confirmed. The in vitro effects of Zn-peptide were better than that of the hexapeptide alone, zinc sulfate alone or 10 µM retinol. In vivo study showed that Zn-peptide significantly reduced the number of the inflammatory lesions, number of skin pores, it also decreased skin redness, sebum level and the amount of protoporphyrin IX corresponding to the C. acnes number. We also observed its anti-ageing effect represented by wrinkle reduction, elasticity improvement and collagen increase. Both the anti-acne and anti-ageing effects of Zn-peptide were better than that of 0.2 % retinol. Moreover, retinol gradually increased TEWL suggesting skin barrier disruption which might contribute to the irritation commonly observed after retinoids application. On the other hand, significantly reduced TEWL values were found after Zn-peptide treatment.
Conclusion:
Zn-peptide proved to be a new, multifunctional compound targeting all key processes involved in acne pathogenesis. It significantly improved appearance of the acne-prone skin and also showed an anti-ageing effect. Its biological activity was better than that of its individual components or retinol. Importantly, Zn-peptide did not show any irritation potential in comparison to retinol.