A Mixture of Topical Forms of Polydeoxyribonucleotide, Vitamin C, and Niacinamide Attenuated Skin Pigmentation and Increased Skin Elasticity by Modulating Nuclear Factor Erythroid 2-like 2
Open accessAbstract
It is well-known that increased oxidative stress caused by ultraviolet B (UV-B) radiation induces melanogenesis and activates metalloproteinases (MMPs), which degrade collagen and elastin fibers, leading to decreased skin elasticity. Various antioxidant agents, such as vitamin C and niacinamide, have been evaluated for use as treatments for photoaging or skin pigmentation. In this study, we evaluated the ability of a topical liquid formula of polydeoxyribonucleotide (PDRN), vitamin C, and niacinamide (PVN) delivered via a microneedling therapy system (MTS) to attenuate photoaging and pigmentation by increasing nuclear factor erythroid 2-like 2 (NRF2)/heme oxygenase-1 (HO-1) and decreasing MMP expression in a UV-B-radiated animal model. The effects of the PVN were compared with those of individual PDRN and hydroquinone (HQ) compounds. The expression of NRF2/HO-1 significantly increased in response to HQ, PDRN, and PVN in UV-B-radiated animal skin. The activity of nicotinamide adenine dinucleotide phosphate hydrogen oxidase decreased in response to HQ, PDRN, and PVN, and the superoxide dismutase activity increased. The expression of tumor protein p53 and microphthalmia-associated transcription factor and tyrosinase activity decreased in response to HQ, PDRN, and PVN, and this decrease was accompanied by decreased melanin content in the skin. The expression of nuclear factor kappa-light-chain enhancer of activated B cells and MMP2/3/9 decreased in response to HQ, PDRN, and PVN in UV-B-radiated skin. However, the expression of collagen type I α1 chain and the amount of collagen fibers that were evaluated by Masson’s trichrome staining increased in response to HQ, PDRN, and PVN. The contents of elastin fibers, fibrillin 1/2 and fibulin 5 increased in response to HQ, PDRN, and PVN. In conclusion, PVN delivered via MTS led to decreased melanogenesis and destruction of collagen and elastin fibers by MMPs, and, thus, PVN decreased skin pigmentation and increased skin elasticity.
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In dermal fibroblasts, PDRN enhances metabolic activity and promotes the synthesis of collagen types I and III through activation of the ERK pathway.
“In dermal fibroblasts, PDRN enhances metabolic activity and promotes the synthesis of essential ECM components—particularly collagen types I and III—through activation of the extracellular signal-regulated kinase (ERK) pathway [52,89,90,91,92,93,94].”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [93]
The Introduction (page unavailable) reports that PDRN enhances fibroblast metabolism and synthesis of dermal matrix components. The Discussion (page unavailable) reports increased collagen type I staining in PDRN-treated animal skin, but it does not establish synthesis of collagen types I and III in dermal fibroblasts. The passages found do not link these effects to ERK activation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPDRN inhibits elastase and MMP-1, preserving elastin integrity, improving skin elasticity, and reducing wrinkle depth.
“Concurrently, it inhibits elastase and matrix metalloproteinase-1 (MMP-1), which are enzymes responsible for ECM degradation, preserving elastin integrity, improving skin elasticity, and reducing wrinkle depth [91,92,93].”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [93]
Involvement of the NRF2 and HO-1 pathways in PDRN's antioxidant effects has been suggested.
“While the exact molecular mechanisms underlying these effects have not been fully elucidated, involvement of the nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) pathways has been suggested [93,136].”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [93]
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The state of the art in anti-aging: plant-based phytochemicals for skin care
Tomaş, M., Günal‐Köroğlu, D., Kamiloğlu, S., Özdal, T., & Çapanoğlu, E. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00498-9 · Cited by 73 · see citing works
Anti-Aging Activity and Modes of Action of Compounds from Natural Food Sources
Song, L., & Zhang, S. (2023) · Biomolecules · doi:10.3390/biom13111600 · Cited by 58 · see citing works
Discovery of matrix metalloproteinase inhibitors as anti-skin photoaging agents
Li, F., Zhi, J., Zhao, R., Sun, Y., Wen, H., Cai, H., Chen, W., Jiang, X., & Bai, R. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116152 · Cited by 46 · see citing works
Park, H. J., Byun, K.-A., Oh, S., Kim, H. M., Chung, M. S., Son, K. H., & Byun, K. (2022) · Molecules · doi:10.3390/molecules27154923 · Cited by 31 · see citing works
Self-citationLee, D., Kim, M. J., Park, H. J., Rah, G. C., Choi, H., Anh, S., Ji, G. H., Kim, M. S., Kim, G. K., Shin, D. W., et al. (2023) · Skin Research and Technology · doi:10.1111/srt.13466 · Cited by 30 · see citing works
Self-citationCarvalho, C. S. C., da Silva, R. D. F., Melo, T. M. V. D. P. E., Inga, A., & Saraiva, L. (2024) · Cancers · doi:10.3390/cancers16233978 · Cited by 28 · see citing works
Developing Plant Exosomes as an Advanced Delivery System for Cosmetic Peptide
Hou, J., Wei, W., Geng, Z., Zhang, Z., Yang, H. L., Zhang, X., Li, L., & Gao, Q. (2024) · ACS Applied Bio Materials · doi:10.1021/acsabm.4c00096 · Cited by 26 · see citing works
Oh, N., Hwang, J., Kang, M. S., Yoo, C.-Y., Kwak, M., & Han, D.-W. (2025) · Biomaterials Research · doi:10.34133/bmr.0183 · Cited by 25 · see citing works
Gulfan, M. C. B., Wanitphakdeedecha, R., Wongdama, S., Jantanapornchai, N., Yan, C., & Rakchart, S. (2022) · Dermatology and Therapy · doi:10.1007/s13555-022-00728-8 · Cited by 23 · see citing works
Recent advances on polydeoxyribonucleotide extraction and its novel application in cosmeceuticals
Nguyen, T. H., Wang, S.-L., & Nguyen, V. B. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.137051 · Cited by 21 · see citing works
Kim, S. T. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17081024 · Cited by 18 · see citing works
Liu, F., Xu, T., He, J., Jiang, Y., Qu, L., Wang, L., Ma, J., Yang, Q., Wu, W., Sun, D., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26715 · Cited by 15 · see citing works
Shu, Z., Ji, Y., Liu, F., Jing, Y., Jiao, C., Li, Y., Zhao, Y., Wang, G., & Zhang, J. (2024) · Marine Drugs · doi:10.3390/md22070325 · Cited by 12 · see citing works
Park, S., Baek, S., Shin, H.-J., Kim, J.-S., Gwon, H.-I., 배승희, & An, S. (2025) · Applied Sciences · doi:10.3390/app151910437 · Cited by 12 · see citing works
Polyglutamate: Unleashing the Versatility of a Biopolymer for Cosmetic Industry Applications
Serra, M., Gudiña, E. J., Botelho, C., Teixeira, J. A., & Barros, A. (2024) · Cosmetics · doi:10.3390/cosmetics11030076 · Cited by 10 · see citing works
Kim, E., Choi, S., Kim, S., Jang, S. J., Lee, S., Kim, H.-I., Jang, J. H., Seo, H. H., Lee, J. H., Choi, S. S., et al. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150335 · Cited by 10 · see citing works
Self-citationJang, S. K., Choi, J., Lim, H. W., Kim, H.-G., & Yoo, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125703 · Cited by 8 · see citing works
Self-citationLee, H. R., Hwa, S., Cho, S., Kim, J.-H., Song, H.-J., Ko, Y., & Park, J. (2024) · Medicina · doi:10.3390/medicina60101610 · Cited by 11 · see citing works
Rušić, D., Ivic, M., Slugan, A., Leskur, D., Modun, D., Durdov, T., Vuković, D., Bukić, J., Božić, J., & Perišin, A. Š. (2024) · Life · doi:10.3390/life14121677 · Cited by 7 · see citing works
PDRN prevents SIRT1 degradation by attenuating autophagy during skin aging
Chen, J., Qiu, F., Shi, J., Huang, W., Zhao, C., & Han, Q. (2025) · PLoS ONE · doi:10.1371/journal.pone.0321005 · Cited by 5 · see citing works
Ye, S., Chen, B., Jeevithan, L., Yang, H., Kong, Y., Diao, X., & Wu, W. (2025) · Journal of Functional Biomaterials · doi:10.3390/jfb16020047 · Cited by 4 · see citing works
Ultraviolet Protection From a Patented Amino Acid Complex Technology
Wu, J. X., Namkoong, J., Goswami, S., Cohen, J. L., & Soliman, N. (2024) · Journal of Drugs in Dermatology · doi:10.36849/jdd.7916 · Cited by 4 · see citing works
Oh, S., Son, M., Jang, J. T., Park, C. H., Son, K. H., & Byun, K. (2022) · International Journal of Endocrinology · doi:10.1155/2022/8486965 · Cited by 4 · see citing works
Self-citationNicotinamide Riboside Ameliorates Hyperpigmentation on Photo-Irradiated Skin
Lee, Y. J., Jang, S. G., Ryu, M. J., & Choi, S. H. (2024) · Cosmetics · doi:10.3390/cosmetics11030073 · Cited by 4 · see citing works
Delgado, C. (2025) · Plastic and Aesthetic Nursing · doi:10.1097/psn.0000000000000635 · Cited by 2 · see citing works
Effects of pine needle essential oil on melanin synthesis in B16F10 cells and its mechanism
Lü, S., Shang, B., Liu, G., Sun, L., Wu, Q., & Geng, Y. (2025) · Biomedical Reports · doi:10.3892/br.2025.2011 · Cited by 1 · see citing works
Lin, Y., Yan, M., Shen, L., Wang, Y., He, H., Han, Z., Chen, H., & Liu, A. (2025) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaf149 · Cited by 1 · see citing works
Expression and Biological Activity of Recombinant Type IV Collagen
Chang, Y., Zhang, Z., Yuwen, W., Ru, X., Fu, R., Zhu, C., Li, W., Duan, Z., & Fan, D. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c02431 · Cited by 1 · see citing works
Chang, Y., Park, J.-Y., Hwang, D., Kim, M. T., Yoon, S., & Cho, S.-H. (2026) · BMC Biotechnology · doi:10.1186/s12896-026-01131-3 · Cited by 1 · see citing works
Photoaging: Update on Pathogenesis, Prevention, and Treatment
Tsai, J., & Kang, S. (2026) · Annals of Dermatology · doi:10.5021/ad.26.006 · Cited by 1 · see citing works
Choi, J., Jang, S. K., Lee, D., & Yoo, Y. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104355 · Cited by 1 · see citing works
Regenerative Aesthetics: Present Advances and Emerging Strategies for Optimized Tissue Health
Cattelan, L., Dayan, S. H., Cohen, S., Muniz, M., & Fabi, S. G. (2026) · Dermatologic Surgery · doi:10.1097/dss.0000000000004985 · Cited by 1 · see citing works
Zafar, T., Khan, H. M. S., Jamil, Q. A., & Ijaz, S. (2026) · Journal of Cosmetic and Laser Therapy · doi:10.1080/14764172.2026.2698114 · Cited by 1 · see citing works
Genetic mutation and aqueous humor metabolites alterations in a family with Marfan syndrome
Wu, J., Li, F., Zhang, J., & Hao, X. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e23696 · Cited by 1 · see citing works
Alotaibi, M. O. (2025) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2025.108594 · Cited by 1 · see citing works
You are what you eat—Or are you? Exploring dietary versus topical antioxidants in skin aging
Dillon, O., Bevan, D., & Gavrilović, J. (2023) · Advances in biogerontology · doi:10.1016/bs.abger.2023.07.003
Investigation of New Potential Uses of Pistacia terebinthus for Various Industries
Asan-Ozusaglam, M. (2023) · Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi · doi:10.18016/ksutarimdoga.vi.1285786
Koldiri, E., Rallis, E. A., & Kefala, V. (2024) · Review of Clinical Pharmacology and Pharmacokinetics - International Edition · doi:10.61873/yaok3799
Oh, G. Y., MD, Kim, H. M., MD, PhD, Oh, S. M., MD, MMBA, Park, M. S., MD, et al. (2025) · Korean Association For Laser Dernatology And Trichology · doi:10.46738/aesthetics.25.0004
Self-citationVITAMINA C EM COSMÉTICOS FACIAIS: CONTRIBUIÇÃO PARA O REJUVENESCIMENTO CUTÂNEO
da Silva, F. F., & dos Santos, V. M. (2025) · Revista Foco · doi:10.54751/revistafoco.v18n11-225
Effectiveness of Vitamin C for Gingival Depigmentation: A Systematic Review
Aljahdali, B., & Dahlan, R. (2026) · International Journal of Dentistry · doi:10.1155/ijod/6980625
Nie, G., Zhang, Y., Wu, X., Luo, Y., Song, H., Li, H., He, Q., Wu, Q., & Chen, R. (2026) · Case Reports in Dermatology · doi:10.1159/000550713
Microagulhamento associado ao Polidesoxirribonucleotideo nas difusões estéticas: revisão narrativa
Brito, N. V. D. S., de Araújo, M. O. C., & Silva, M. S. (2026) · Revista Multidisciplinar do Nordeste Mineiro · doi:10.66104/ryvhdg20
Kim, H. J., Lee, J. W., Kim, S., & Son, K. H. (2026) · Journal of Functional Biomaterials · doi:10.3390/jfb17070351
Self-citationRho, N., Jeon, H. D., & Park, H.-J. (2026) · Cosmetics · doi:10.3390/cosmetics13050248
Self-citationFedorov, P. G., Георгиевна, П. Т., Danilov, A. A., Pelishenko, O. L., & Корчажкина, Н. Б. (2026) · Fizioterapevt (Physiotherapist) · doi:10.33920/med-14-2604-11
Park, J., Im, D., Park, S., Shin, H., & Park, D. (2026) · Cosmetics · doi:10.3390/cosmetics13050272
BindingDB (2025) · UC San Diego · doi:10.7270/q2hd818f
- Authors
- Kim, H. M., Byun, K.-A., Oh, S., Yang, J. Y., Park, H. J., Chung, M. S., Son, K. H., & Byun, K.
- Affiliations
- Gachon University (KR)
- Maylin Anti-Aging Center Apgujeong, Seoul 06005, Korea
- I’ll Global Co., Inc., Seoul 06532, Korea
- Corresponding author
- Son, Kuk Hui
- Byun, Kyunghee
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2022-02-14
- Volume
- 27
- Issue
- 4
- Pages
- 1276
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8879610
- OpenAlex
- W4212831473
- Cited by
- 48
- References
- 90
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 13 · 2023: 5 · 2022: 3
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- I`ll Global Inc. Co. (2021 01 290001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- polydeoxyribonucleotide, vitamin C, nicotinamide, skin pigmentation, skin elasticity, photoaging, UV-B radiation, Nrf2/HO-1 pathway, heme oxygenase-1, matrix metalloproteinases, melanogenesis, collagen degradation, elastin fibers, superoxide dismutase, NADPH oxidase, hydroquinone, tyrosinase, p53, MAF, nuclear factor-kappaB
- MeSH terms
- Ascorbic Acid, Elasticity, Immunohistochemistry, Melanins, Niacinamide, Polydeoxyribonucleotides, Skin, Skin Physiological Phenomena, Skin Pigmentation, Ultraviolet Rays, Biomarkers, Gene Expression, Matrix Metalloproteinases, NF-E2-Related Factor 2
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