Polydeoxyribonucleotide Mitigates UVB-Induced Skin Photoaging in Hairless Mice : Polydeoxyribonucleotide의 UVB 유발 Hairless 마우스 피부 광노화 억제효과

다국어 초록 (Multilingual Abstract)

Repeated exposure of skin to ultraviolet (UV) radiation induces photoaging, a progressive deterioration of skin structure and function characterized by collagen degradation, abnormal accumulation of elastic fibers, and increased glycosaminoglycans, ultimately resulting in wrinkles, loss of elasticity, dryness, and pigment imbalance. Polydeoxyribonucleotide (PDRN), a polymer of deoxyribonucleotides derived from salmonid fish sperm, exhibits tissue-regenerative activity through its anti-inflammatory, pro-proliferative, and angiogenic properties. This study evaluated the dose-dependent topical effects of PDRN (0.25%, 0.5%, 1%) and compared them with 1% L-ascorbic acid (L-AA) in a UVB-induced photoaging model using SKH1-hr hairless mice.
Photoaging was induced by exposing mice to 0.18 J/cm² of UVB three times weekly for 15 weeks. Test substances (PDRN 0.25%, 0.5%, 1% and L-AA 1%) were dissolved in 0.5% carboxymethylcellulose (CMC) and applied topically (200 μL/mouse/day) throughout the 15-week period. Wrinkle formation, skin edema, and body weight were recorded. Anti-inflammatory effects were assessed by measuring MPO activity and IL-1β and IL-10 levels. Oxidative stress was evaluated by quantifying GSH content, lipid peroxidation (MDA), superoxide production, and the mRNA expression of Nox2, GSH reductase, TGF-β1, p38 MAPK, AKT, and MMP-1/9/13 using quantitative RT-PCR. Immunohistochemistry was performed for MMP-9, nitrotyrosine (NT), 4-hydroxynonenal (4-HNE), cleaved caspase-3, and PARP. Skin hydration, type I collagen (COL1), hyaluronan content, and the expression of Has1/2/3 and COL1A1/A2 were measured to assess moisturizing and ECM-regenerative effects. Six groups (n = 10/group) were used: intact control, UVB control, L-AA 1%, PDRN 1%, PDRN 0.5%, and PDRN 0.25%.
Chronic UVB exposure markedly aggravated skin wrinkles, increased epidermal thickness, inflammatory cell infiltration, and collagen disorganization. MPO activity, IL-1β, MDA, superoxide production, and MMP-1/9/13 expression were significantly elevated, whereas TGF-β1, GSH reductase, COL1, hyaluronan content, and skin hydration were significantly reduced. Strong immunopositivity for NT, 4-HNE, MMP-9, cleaved caspase-3, and PARP confirmed oxidative stress–mediated apoptosis and ECM degradation.
Topical PDRN significantly and dose-dependently attenuated UVB-induced photoaging changes. The 0.5% PDRN formulation showed efficacy comparable to 1% L-AA, improving antioxidant status, reducing inflammation and apoptosis, inhibiting MMP activity, and enhancing ECM synthesis and hydration. PDRN also increased TGF-β1 and Has1/2/3 expression while suppressing p38 MAPK, AKT, and MMP expression, demonstrating multi-pathway protective effects.
In conclusion, topical PDRN mitigates UVB-induced photoaging through antioxidative, anti-inflammatory, anti-apoptotic, and ECM-preserving mechanisms. The comparable efficacy of 0.5% PDRN to 1% L-ascorbic acid highlights its potential as a promising functional ingredient for anti-photoaging skincare products, moisturizers, and therapeutic ointments.

목차 (Table of Contents)

• 1. Introduction 1
• 2. Materials and Methods 4
• 2.1 Animals and Husbandry 4
• 2.2 UVB Irradiation 6
• 2.3 Preparation and Administration of Test Materials 6
• 2.4 Measurement of Body Weights 7
• 2.5 Replica Generation and Wrinkle Analysis 8
• 2.6 Edema Evaluation 8
• 2.7 Determination of Skin Water Content 8
• 2.8 Measurement of Collagen Type I Content 9
• 2.9 Quantification of Hyaluronan 9
• 2.10 Myeloperoxidase (MPO) Activity 9
• 2.11 Cytokine Quantification (IL-1β, IL-10) 10
• 2.12 Determination of GSH Levels 10
• 2.13 Lipid Peroxidation Assay (MDA) 10
• 2.14 Superoxide Anion Measurement 11
• 2.15 Quantitative PCR Analysis 11
• 2.16 Histopathology 12
• 2.17 Immunohistochemistry. 13
• 2.18 Statistical Analyses 14
• 3. Results 16
• 3.1 Body Weight and Gains 16
• 3.2 Wrinkle Measurement 18
• 3.3 UVB-Induced Skin Edema 22
• 3.4 Skin Water Content 24
• 3.5 Collagen Type I Content 25
• 3.6 Hyaluronan Levels 25
• 3.7 MPO Activity 26
• 3.8 IL-1β Levels 27
• 3.9 IL-10 Levels 28
• 3.10 GSH Levels 28
• 3.11 Lipid Peroxidation (MDA) 30
• 3.12 Superoxide Anion Production 30
• 3.13 qPCR analysis 31
• 3.14 Histopathology 38
• 4. Discussion 50
• 5. Conclusion 67
• References 69
• List of Tables 82
• List of Figures 83
• Abstract 84
• Abstract in Korean 86