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. 2025 Jan;15(1):189-200.
doi: 10.1007/s13555-024-01332-8. Epub 2024 Dec 25.

Effects of Retinol, Natural Pea Peptide and Antioxidant Blend in a Topical Formulation: In Vitro and Clinical Evidence

Brian Cook  1 , Melanie Riggs  1 , K C Holley  1 , Helen Knaggs  1 , Ganesh Diwakar  1 , Edwin D Lephart  2
Affiliations

Effects of Retinol, Natural Pea Peptide and Antioxidant Blend in a Topical Formulation: In Vitro and Clinical Evidence

Brian Cook et al. Dermatol Ther (Heidelb). 2025 Jan.

Abstract

Introduction: Retinol has a long history of treating skin conditions, including photoaging. However, skin irritation with repeated use of retinol is well documented. The present study assessed the effectiveness of a novel topical formulation, referred to as retinol topical formulation (RTF), to improve the quality of skin health. The RTF was composed of a low dose retinol, a synthetic retinoid ester, a pea peptide, and an antioxidant blend.

Methods: In vitro assessment of RTF on human skin co-cultures (human keratinocytes, melanocytes, and dermal fibroblasts) identified gene expression levels and skin biomarkers after 24 h exposure. An 8-week clinical study was conducted to evaluate once-nightly application of the RTF for short-term and long-term benefits in 30 adult subjects between 35 and 70 years of age (21 female, 9 male). Skin evaluations were conducted via bioinstrumentation (for hydration, transepidermal water loss and elasticity) and at 0, 1-, 2-, 4-, and 8-week self-assessment questionnaires and photo-imaging analysis were performed.

Results: RTF treatment of skin in vitro co-cultures upregulated aquaporin-3, PER1, collagen, and elastin, and downregulated expression of MMP1 and the pigmentation genes TYRP1 and MITF. The clinical assessment significantly improved hydration, transepidermal water loss, and elasticity along with incremental but significant increases in nine skin parameters (hydration, clarity, radiance/glow, smoothness, brightness, texture, appearance of pores, dark spots/hyperpigmentation, and skin tone evenness from baseline) with continuous use over 8 weeks compared to baseline values.

Conclusions: The RTF in vitro analysis showed significant positive changes for several skin biomarkers, and the clinical assessment showed RTF significantly improved the visible signs of dermal aging, without irritation.

Keywords: Antiaging; Antioxidant; Clinical; Formulation; In vitro; Pea peptide; Rejuvenation; Retinoid analogues; Retinol; Skin.

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Conflict of interest statement

Declarations. Conflict of Interest: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of date; in writing of the manuscript; or in the decision to publish the results. Brian Cook, Melanie Riggs, K.C. Holley, Helen Knaggs and Ganesh Diwakar are employed by NSE Inc. Edwin Lephart is an Editorial Board member of Dermatology and Therapy. Edwin Lephart was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: This clinical study was approved by the Allendale Institutional Review Board on March 21, 2024, with the assigned study number (NSE-18-24). The study was conducted in accordance with the ethical principles of the 1975 Declaration of Helsinki and its subsequent amendments [37]. Prior to the performance of any study-specific procedures, subjects were provided with an explanation of the nature of the study, including the purpose, procedures, expected duration, and potential risk. Prospective subjects were informed of their right to withdraw from the study at any time without being obliged to give a reason. If consent was obtained, the subject signed and dated the informed consent form. Specific written consent to use the patient’s facial photos was obtained.

Figures

Fig. 1
Fig. 1
RTF treatment on skin rejuvenation and skin renewal activity. RTF treatment upregulated collagen and elastin and downregulated MMP1 (matrix metalloproteinase 1) expression. RTF also upregulated AQP3 (hydration gene), PER1 (a circadian rhythm marker), and downregulated TYRP1 (encoding a rate-limiting enzyme in melanin biosynthesis) and MITF (transcription factor, master regulator of pigmentation genes). RTF was added to cells in triplicate for assay of each of the genes. Data is shown as % upregulation/downregulation ± SEM for each gene. ► Significant change in gene expression in RTF-treated samples compared to vehicle control
Fig. 2
Fig. 2
Subjects self-perception assessment of skin attributes at week 1, 2, 4, and 8
Fig. 3
Fig. 3
Representative images of two subjects, one male (A) and one female (B), showing improvement in skin hydration, radiance, hydration, clarity, radiance/glow, smoothness, brightness, texture, and skin tone evenness from baseline immediately after retinol-peptide application and progressive improvements in skin attributes from week 1 to week 8
See this image and copyright information in PMC

References

    1. Ramos-E-Silva M, Hahn DM, Rutowitsch MS, Zechneister M. Hydroxy acids and retinoids in cosmetics. Clin Dermatol. 2001;19:460–6. - DOI - PubMed
    1. Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Intervent Aging. 2006;1:327–48. - DOI - PMC - PubMed
    1. Temova Rakusa Z, Skufca P, Kristl A, Roskar R. Retinoid stability and degradation kinetics in commercial cosmetic products. J Cosmet Dermatol. 2021;20:2350–8. - DOI - PubMed
    1. Antille C, Tran C, Sorg O, Saurat J-H. Penetration and metabolism of topical retinoids in ex-vivo organ-cultured full-thickness human skin explants. Skin Pharmacol Physiol. 2004;17:124–8. - DOI - PubMed
    1. Szymanski L, Skopek R, Palusinska M, et al. Retinoic acid and is derivatives in skin. Cells. 2020;9:2660. - DOI - PMC - PubMed

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