{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:59:11Z","timestamp":1792803551169,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Student Scientific Society of Poznan University of Medical Sciences","award":["316\/2018"],"award-info":[{"award-number":["316\/2018"]}],"id":[{"id":"https:\/\/ror.org\/02zbb2597","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Photoaging is a process related to an increased level of reactive oxygen species (ROS). Polyphenols can scavenge free radicals in the body, which can delay skin aging. Therefore, our work aimed to prepare a biologically active extract from dry fruits of Vaccinium myrtillus or Vaccinium corymbosum and use it for the preparation of hydrogels for topical application. Therefore, eight different extracts (using V. myrtillus and V. corymbosum and different extraction mixtures: methanol, methanol\u2013water 1:1, water, acetone\u2013water 1:1) were prepared and their phytochemical (total polyphenolic content, total flavonoid content, total anthocyanin content) and biological properties (antioxidant, anti-hyaluronidase, and anti-tyrosinase activity) were assessed. Cytotoxicity towards HaCaT keratinocytes was also determined. Based on the results, the acetone\u2013water extract from V. myrtillus was selected for further study. Using the Design of Experiments approach, chitosan-based hydrogels with bilberry fruit extract were prepared. The content of extract and chitosan were selected as independent factors. The activity of hydrogels depended on the extract content; however, the enzyme-inhibiting (anti-hyaluronidase and anti-tyrosinase) activity resulted from the presence of both the extract and chitosan. Increased concentration of chitosan in the hydrogel base led to increased viscosity of the hydrogel and, consequently, a slower release of active compounds. To get optimal hydrogel characteristics, 1% extract and 2.5% MMW chitosan were utilized. The research suggests the validity of using bilberry fruit extracts in topical preparations with anti-aging properties.<\/jats:p>","DOI":"10.3390\/antiox13010105","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T07:25:07Z","timestamp":1705303507000},"page":"105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Anti-Aging Properties of Chitosan-Based Hydrogels Rich in Bilberry Fruit Extract"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-1766","authenticated-orcid":false,"given":"El\u017cbieta","family":"Studzi\u0144ska-Sroka","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-9336","authenticated-orcid":false,"given":"Magdalena","family":"Paczkowska-Walendowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2088-2508","authenticated-orcid":false,"given":"Cansu","family":"Erdem","sequence":"additional","affiliation":[{"name":"Department Pharmaceutical Chemistry, Ege \u00dcniversitesi, 35040 \u0130zmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-7549","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Paluszczak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3 Str, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6607-7436","authenticated-orcid":false,"given":"Robert","family":"Kleszcz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3 Str, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Hoszman-Kulisz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-5419","authenticated-orcid":false,"given":"Judyta","family":"Cielecka-Piontek","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00011-022-01598-8","article-title":"Photoaging: UV Radiation-Induced Inflammation and Immunosuppression Accelerate the Aging Process in the Skin","volume":"71","author":"Salminen","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1517\/13543776.2014.1000863","article-title":"Natural Compounds for Solar Photoprotection: A Patent Review","volume":"25","author":"Serafini","year":"2015","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.freeradbiomed.2016.10.488","article-title":"Oxidatively-Generated Damage to DNA and Proteins Mediated by Photosensitized UVA","volume":"107","author":"Brem","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.ijbiomac.2018.09.188","article-title":"Hyaluronic Acid, a Promising Skin Rejuvenating Biomedicine: A Review of Recent Updates and Pre-Clinical and Clinical Investigations on Cosmetic and Nutricosmetic Effects","volume":"120","author":"Bukhari","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111735","DOI":"10.1016\/j.indcrop.2019.111735","article-title":"Anti-Aging Potential and Anti-Tyrosinase Activity of Three Hypericum Species with Focus on Phytochemical Composition by LC\u2013MS\/MS","volume":"141","author":"Ersoy","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liu, H.-M., Cheng, M.-Y., Xun, M.-H., Zhao, Z.-W., Zhang, Y., Tang, W., Cheng, J., Ni, J., and Wang, W. (2023). Possible Mechanisms of Oxidative Stress-Induced Skin Cellular Senescence, Inflammation, and Cancer and the Therapeutic Potential of Plant Polyphenols. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043755"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ansary, T.M., Hossain, M.R., Kamiya, K., Komine, M., and Ohtsuki, M. (2021). Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083974"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Paj\u0105k, J., Nowicka, D., and Szepietowski, J.C. (2023). Inflammaging and Immunosenescence as Part of Skin Aging\u2014A Narrative Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097784"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/ics.12728","article-title":"Oxidative Stress in the Skin: Impact and Related Protection","volume":"43","author":"Chen","year":"2021","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_10","unstructured":"(2023, December 29). Melanin and Lipofuscin as Hallmarks of Skin Aging. Available online: https:\/\/www.termedia.pl\/Melanin-and-lipofuscin-as-hallmarks-of-skin-aging,7,29785,0,1.html."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/jocd.13093","article-title":"Polyphenols as Natural Antioxidants in Cosmetics Applications","volume":"19","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tundis, R., Tenuta, M.C., Loizzo, M.R., Bonesi, M., Finetti, F., Trabalzini, L., and Deguin, B. (2021). Vaccinium Species (Ericaceae): From Chemical Composition to Bio-Functional Activities. Appl. Sci., 11.","DOI":"10.3390\/app11125655"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e06297","DOI":"10.1016\/j.heliyon.2021.e06297","article-title":"Phenolic Compounds of Blueberries (Vaccinium spp.) as a Protective Strategy against Skin Cell Damage Induced by ROS: A Review of Antioxidant Potential and Antiproliferative Capacity","volume":"7","year":"2021","journal-title":"Heliyon"},{"key":"ref_14","first-page":"399","article-title":"Comparative Study of Anthocyanin Composition, Antimicrobial and Antioxidant Activity in Bilberry (Vaccinium myrtillus L.) and Blueberry (Vaccinium corymbosum L.) Fruits","volume":"66","author":"Burdulis","year":"2009","journal-title":"Acta Pol. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.3390\/cimb44100313","article-title":"Anti-Inflammatory Activity of Bilberry (Vaccinium myrtillus L.)","volume":"44","author":"Sharma","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s11357-012-9412-z","article-title":"Blueberry Consumption Prevents Loss of Collagen in Bone Matrix and Inhibits Senescence Pathways in Osteoblastic Cells","volume":"35","author":"Zhang","year":"2013","journal-title":"Age"},{"key":"ref_17","first-page":"e24856","article-title":"Collagen Structure, Synthesis, and Its Applications: A Systematic Review","volume":"14","author":"Shenoy","year":"2022","journal-title":"Cureus"},{"key":"ref_18","first-page":"1","article-title":"Chitosan Based Hydrogels: Characteristics and Pharmaceutical Applications","volume":"10","author":"Ahmadi","year":"2015","journal-title":"Res. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xia, Y., Wang, D., Liu, D., Su, J., Jin, Y., Wang, D., Han, B., Jiang, Z., and Liu, B. (2022). Applications of Chitosan and Its Derivatives in Skin and Soft Tissue Diseases. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.894667"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.ijbiomac.2019.04.052","article-title":"Biodegradable Antioxidant Chitosan Films Useful as an Anti-Aging Skin Mask","volume":"132","author":"Afonso","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Studzi\u0144ska-Sroka, E., Galanty, A., Go\u015bciniak, A., Wieczorek, M., K\u0142aput, M., Dudek-Makuch, M., and Cielecka-Piontek, J. (2021). Herbal Infusions as a Valuable Functional Food. Nutrients, 13.","DOI":"10.3390\/nu13114051"},{"key":"ref_22","unstructured":"(2023, December 29). Polish Pharmacopoeia|Urz\u0105d Rejestracji Produkt\u00f3w Leczniczych, Wyrob\u00f3w Medycznych i Produkt\u00f3w Biob\u00f3jczych, Available online: https:\/\/www.urpl.gov.pl\/en\/polish-pharmacopoeia."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Paczkowska-Walendowska, M., Go\u015bciniak, A., Szymanowska, D., Szwajgier, D., Baranowska-W\u00f3jcik, E., Szulc, P., Dreczka, D., Simon, M., and Cielecka-Piontek, J. (2021). Blackberry Leaves as New Functional Food? Screening Antioxidant, Anti-Inflammatory and Microbiological Activities in Correlation with Phytochemical Analysis. Antioxidants, 10.","DOI":"10.3390\/antiox10121945"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Studzi\u0144ska-Sroka, E., Majchrzak-Celi\u0144ska, A., Zalewski, P., Szwajgier, D., Baranowska-W\u00f3jcik, E., \u017barowski, M., Plech, T., and Cielecka-Piontek, J. (2021). Permeability of Hypogymnia Physodes Extract Component-Physodic Acid through the Blood-Brain Barrier as an Important Argument for Its Anticancer and Neuroprotective Activity within the Central Nervous System. Cancers, 13.","DOI":"10.3390\/cancers13071717"},{"key":"ref_25","first-page":"597","article-title":"Cladonia Uncialis as a Valuable Raw Material of Biosynthetic Compounds against Clinical Strains of Bacteria and Fungi","volume":"66","author":"Tomczak","year":"2019","journal-title":"Acta Biochim. Pol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1023\/A:1015812615635","article-title":"A Simple Rheological Method for the In Vitro Assessment of Mucin-Polymer Bioadhesive Bond Strength","volume":"7","author":"Hassan","year":"1990","journal-title":"Pharm. Res."},{"key":"ref_27","unstructured":"(2023, December 29). Full Article: Anthocyanins Profiling of Bilberry (Vaccinium myrtillus L.) Extract That Elucidates Antioxidant and Anti-Inflammatory Effects. Available online: https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/09540105.2021.1986471."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fraisse, D., Bred, A., Felgines, C., and Senejoux, F. (2020). Screening and Characterization of Antiglycoxidant Anthocyanins from Vaccinium Myrtillus Fruit Using DPPH and Methylglyoxal Pre-Column HPLC Assays. Antioxidants, 9.","DOI":"10.3390\/antiox9060512"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.2174\/1389557519666190906115619","article-title":"Hyaluronan Fragmentation during Inflammatory Pathologies: A Signal That Empowers Tissue Damage","volume":"20","author":"Avenoso","year":"2020","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113059","DOI":"10.1016\/j.indcrop.2020.113059","article-title":"Anti-Aging Potential, Anti-Tyrosinase and Antibacterial Activities of Extracts and Compounds Isolated from Rosa Chinensis Cv. \u2018JinBian\u2019","volume":"159","author":"Li","year":"2021","journal-title":"Ind. Crops Prod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2174\/187220810791110732","article-title":"Genus Vaccinium: Medicine, Cosmetics, and Coatings","volume":"4","author":"Johnson","year":"2010","journal-title":"Recent Pat. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1039\/C7FO01205E","article-title":"Anthocyanin Profile, Antioxidant Activity and Enzyme Inhibiting Properties of Blueberry and Cranberry Juices: A Comparative Study","volume":"8","author":"Les","year":"2017","journal-title":"Food Funct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9571490","DOI":"10.1155\/2020\/9571490","article-title":"Blueberry Extracts as a Novel Approach to Prevent Ozone-Induced Cutaneous Inflammasome Activation","volume":"2020","author":"Pambianchi","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_34","unstructured":"(2023, December 29). Protective Effect of Vaccinium myrtillus Extract against UVA- and UVB-Induced Damage in a Human Keratinocyte Cell Line (HaCaT Cells)\u2014ScienceDirect. Available online: https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S1011134414000220?via%3Dihub."},{"key":"ref_35","unstructured":"Preedy, V.R., and Patel, V.B. (2021). Cancer, Academic Press. [2nd ed.]."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Andr\u00e9s, C.M.C., P\u00e9rez de la Lastra, J.M., Juan, C.A., Plou, F.J., and P\u00e9rez-Lebe\u00f1a, E. (2023). Polyphenols as Antioxidant\/Pro-Oxidant Compounds and Donors of Reducing Species: Relationship with Human Antioxidant Metabolism. Processes, 11.","DOI":"10.3390\/pr11092771"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8996","DOI":"10.1038\/srep08996","article-title":"Bilberry Extract (Antho 50) Selectively Induces Redox-Sensitive Caspase 3-Related Apoptosis in Chronic Lymphocytic Leukemia Cells by Targeting the Bcl-2\/Bad Pathway","volume":"5","author":"Alhosin","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_38","unstructured":"(2023, December 29). Frontiers|The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review. Available online: https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.943911\/full."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbrc.2021.10.057","article-title":"Impact of Chlorogenic Acid on Modulation of Significant Genes in Dermal Fibroblasts and Epidermal Keratinocytes","volume":"583","author":"Lee","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Paczkowska-Walendowska, M., and Cielecka-Piontek, J. (2022). Chitosan as a Functional Carrier for the Local Delivery Anti-Inflammatory Systems Containing Scutellariae Baicalensis Radix Extract. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102148"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hua, Y., Ma, C., Wei, T., Zhang, L., and Shen, J. (2020). Collagen\/Chitosan Complexes: Preparation, Antioxidant Activity, Tyrosinase Inhibition Activity, and Melanin Synthesis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010313"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"136093","DOI":"10.1016\/j.foodchem.2023.136093","article-title":"Preparation, Antioxidant and Tyrosinase Inhibitory Activities of Chitosan Oligosaccharide-Hydroxypyridinone Conjugates","volume":"420","author":"Zhang","year":"2023","journal-title":"Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kaczmarek-Szczepa\u0144ska, B., Mazur, O., Michalska-Sionkowska, M., \u0141ukowicz, K., and Osyczka, A.M. (2021). The Preparation and Characterization of Chitosan-Based Hydrogels Cross-Linked by Glyoxal. Materials, 14.","DOI":"10.3390\/ma14092449"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Manzanara P\u00e9rez, C., Torres-Pab\u00f3n, N.S., Laguna, A., Torrado, G., de la Torre-Iglesias, P.M., Torrado-Santiago, S., and Torrado-Salmer\u00f3n, C. (2023). Development of Chitosan\/Sodium Carboxymethylcellulose Complexes to Improve the Simvastatin Release Rate: Polymer\/Polymer and Drug\/Polymer Interactions\u2019 Effects on Kinetic Models. Polymers, 15.","DOI":"10.3390\/polym15204184"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"119100","DOI":"10.1016\/j.carbpol.2022.119100","article-title":"Chitosan Based Bioadhesives for Biomedical Applications: A Review","volume":"282","author":"Hamedi","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.actbio.2017.01.065","article-title":"A Novel Injectable Tissue Adhesive Based on Oxidized Dextran and Chitosan","volume":"53","author":"Balakrishnan","year":"2017","journal-title":"Acta Biomater."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/1\/105\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:47:12Z","timestamp":1760104032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/1\/105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["antiox13010105"],"URL":"https:\/\/doi.org\/10.3390\/antiox13010105","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,15]]}}}