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. 2024 Dec;14(12):3321-3336.
doi: 10.1007/s13555-024-01298-7. Epub 2024 Nov 7.

Evaluation of the Biological Effect of a Nicotinamide-Containing Broad-Spectrum Sunscreen on Photodamaged Skin

Teresa Torres-Moral  1   2 , Gemma Tell-Martí  1   2 , Jaume Bague  2 , Pau Rosés-Gibert  2 , Neus Calbet-Llopart  1   2 , Judit Mateu  2 , Javiera Pérez-Anker  2   3 , Míriam Potrony  1   4 , Beatriz Alejo  2 , Pablo Iglesias  2 , Natalia Espinosa  4 , Carmen Orte Cano  5 , Elisa Cinotti  6 , Véronique Del Marmol  5 , Margot Fontaine  5 , Makiko Miyamoto  5 , Jilliana Monnier  7 , Jean Luc Perrot  8 , Pietro Rubegni  6 , Linda Tognetti  6 , Mariano Suppa  5   9 , Anne Laure Demessant-Flavigny  10 , Caroline Le Floc'h  10 , Leonor Prieto  11 , Josep Malvehy  1   2   3 , Susana Puig  12   13   14
Affiliations

Evaluation of the Biological Effect of a Nicotinamide-Containing Broad-Spectrum Sunscreen on Photodamaged Skin

Teresa Torres-Moral et al. Dermatol Ther (Heidelb). 2024 Dec.

Abstract

Introduction: UVA-UVB increases skin matrix metalloproteinases and breaks down extracellular proteins and fibrillar type 1 collagen, leading to photodamage. Topical application of nicotinamide prevents UV-induced immunosuppression. Several studies have demonstrated the importance of protection against UV. This study aims to determine the biological effect of a high broad-spectrum UVB-UVA sunscreen containing nicotinamide and panthenol (SSNP) on photodamaged skin using linear confocal optical coherence tomography (LC-OCT), immunohistochemistry, and RNA profiling.

Methods: Two areas of severely photodamaged forearm skin (L01 and L02) and one less sun-damaged (naturally protected) area on the inner part of the forearm (L03) were identified in 14 subjects. These areas were imaged using LC-OCT and L01 and L03 were biopsied at baseline. After 4 weeks of treatment with SSNP, L02 was reimaged using LC-OCT, and biopsied. Histology, immunostaining with p21, p53, PCNA, and CPD, and RNA sequencing were performed in all samples.

Results: LC-OCT analysis showed that epidermis thickness and the number of keratinocytes is higher in the sun-exposed areas than in the non-exposed areas. Comparing before and after treatment, even though there is a trend towards normalization, the differences were not statistically significant. The expression of p21, PCNA, p53, and CPD increased in severely photodamaged skin compared to less-damaged skin. When comparing before and after treatment, only p21 showed a trend to decrease expression. RNA sequencing analysis identified 1552 significant genes correlating with the progression from non-visibly photodamaged skin to post-treatment and pre-treatment samples; in the analysis comparing pre- and post-treatment samples, 5429 genes were found to be significantly associated. A total of 1115 genes are common in these two analyses. Additionally, nine significant genes from the first analysis and eight from the second are related to collagen. Six of these collagen genes are common in the two analyses. MAPK and cGMP-PKG signalling pathways are upregulated in the progression to photodamage analysis. In the pre- and post-treatment analysis, 32 pathways are downregulated after treatment, the most statistically significant being the ErbB, Hippo, NOD-like receptor, TNF, and NF-kB signalling pathways.

Conclusion: This study demonstrates the role of SSNP in collagen generation, highlights the relevance of the cGMP-PKG and MAPK signalling pathways in photodamage, and shows the ability of SSNP to downregulate pathways activated by UV exposure. Additionally, it deepens our understanding of the effect of SSNP on immune-related pathways.

Keywords: Collagen; Nicotinamide; Photodamage.

Plain language summary

This study focuses on the damage that sun exposure can do to our skin, also called photodamage. This damage is mainly caused by ultraviolet radiation, which can lead to problems such as wrinkles, changes in skin color, and sagging skin. Nicotinamide, a form of vitamin B3, helps our cells repair their DNA and prevents them from dying. Previous studies in mice have shown that nicotinamide can protect the immune system against photodamage and reduce the risk of cancer. In order to understand how sunscreen containing nicotinamide and panthenol affects photodamage, an international team of researchers gathered 14 Catalan participants and examined severely sun-damaged skin areas and less sun-damaged skin. We conducted imaging, molecular, and genetic experiments before and after 4 weeks of nicotinamide sunscreen use. The results show that severely sun-damaged skin is thicker and contains more cells called keratinocytes. Additionally, certain indicators of DNA damage and repair are more active in severely sun-damaged skin. Genetic analyses reveal that the photodamage process causes significant differences in certain genetic pathways such as cGMP-PKG and MAPK pathways. Using nicotinamide sunscreen leads to positive changes in several cellular processes, including the way cells divide, respond to stress, and produce collagen. In summary, this study gives us a deeper understanding of skin photodamage and underlines the potential benefits of adding nicotinamide to sunscreens, which could be a promising way to reduce the damage caused by UV radiation.

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Conflict of interest statement

Declarations. Conflict of Interest: All authors declare some conflict of interest since La Roche-Posay funded this study. Moreover, Anne Laure Demessant-Flavigny, Leonor Prieto and Caroline Le Floc’h are L’Oreal Employees. In the last 36 months, existing conflict of interests were: Véronique Del Marmol have grants or contracts from BMS, MSD, Almirall and Sanofia; Josep Malvehy and Susana Puig from Abbvie, Almirall, Amgen, BMS, Biofrontera, Canfield, Cantabria, Fotofinder, GSK, ISDIN, La Roche Posay, Leo Pharma, MSD, MEDA, Novartis, Polychem, Roche and Sun Pharma. Véronique Del Marmol has received consulting fees from BMS, MSD, Sanofi, Merck, Almirall, Abbvie, Leo pharma, Pierre fabre, andNovartis. Josep Malvehy and Susana Puig have received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Roche Posay, Pierre-Fabre, Almirall and ISDIN; Jilliana Monnier from BMS, Pierre Fabre and Novartis; MP from ISDIN; Véronique Del Marmol from BMS, MSD,Sanofi, Sun pharma, Pierre fabre and Novartis. Josep Malvehy and Susana Puig received support for attending meetings and/or travel from Roche Posay, Pierre-Fabre, Almirall and ISDIN; Véronique Del Marmol from BMS, MSD, Pierre Fabre and Novartis; Josep Malvehy and Susana Puig participated on a Data Safety Monitoring Board Advisory Board for Pierre-Fabre, Almirall, SunPharma. Josep Malvehy and Susana Puig have stock options in Athena Tech of Dermavision. Ethical Approval: The study was approved in November 2019 by the Ethics Committee of Hospital Clínic de Barcelona, Spain (Nº HCB20190849). This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The patients who took part in the study have given written informed consent to the publication of their case details.

Figures

Fig. 1
Fig. 1
Principal component analysis (a) and heatmap (b) of photodamage analysis from less sun-damaged to pre-treated photodamaged skin. L03 less sun-damaged samples, L02 photodamaged post-treatment samples, L01 photodamaged pre-treatment samples
See this image and copyright information in PMC

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