{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:48:02Z","timestamp":1782362882097,"version":"3.54.5"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004166","name":"Warszawski Uniwersytet Medyczny","doi-asserted-by":"publisher","award":["WF4L\/1\/F\/MG\/N\/25\/25"],"award-info":[{"award-number":["WF4L\/1\/F\/MG\/N\/25\/25"]}],"id":[{"id":"10.13039\/501100004166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Birch witches\u2019 broom is an abnormal plant structure caused by infection of birch trees with the dimorphic fungus\n                      <jats:italic>Taphrina betulina<\/jats:italic>\n                      Rostr., (1883). Although classified as a disease, witches\u2019 broom has traditionally been used in folk medicine to treat skin disorders. This suggests that fungal infection may induce metabolic reprogramming in host tissues, leading to the production and accumulation of biologically active secondary metabolites. We hypothesized that infection-driven metabolic changes in witches\u2019 broom tissue could generate compounds capable of modulating keratinocyte viability, migration, and inflammatory responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Aqueous extracts from witches\u2019 broom and healthy birch branches were analyzed by UHPLC-DAD-MS\n                      <jats:sup>n<\/jats:sup>\n                      . Biological activity was assessed\n                      <jats:italic>in vitro<\/jats:italic>\n                      using human keratinocytes (HaCaT) and melanoma cells (HTB-140). Cytotoxicity was determined by MTT assay, keratinocyte migration by scratch assay, pro-inflammatory cytokines IL-6\/IL-8 by ELISA, and antimicrobial activity by disc diffusion against skin pathogens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Phytochemical profiling revealed qualitative differences, particularly in flavonoids, phenolic acids, and diarylheptanoids. Cytotoxicity showed concentration-dependent effects. The IC\n                      <jats:sub>50<\/jats:sub>\n                      values for witches\u2019 broom and healthy birch extracts were 260.9\u00a0\u00b5g\/mL and 327.1\u00a0\u00b5g\/mL in HaCaT cells, and 487.5\u00a0\u00b5g\/mL and 453\u00a0\u00b5g\/mL in HTB-140 cells, respectively. Keratinocyte migration was examined using a scratch assay. After 48\u00a0h, witches\u2019 broom extract inhibited HaCaT cell migration by 99.09% \u00b1 4.71% at the highest tested concentration, compared to 84.33% \u00b1 5.14% inhibition by the healthy birch extract. Witches\u2019 broom extract significantly reduced IL-6 secretion in stimulated HaCaT cells, while showing limited effect on IL-8 production. Antimicrobial activity against skin-associated pathogens revealed selective\n                      <jats:italic>C. acnes<\/jats:italic>\n                      inhibition by witches\u2019 broom extract.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>This study provides the first direct comparison of their phytochemical composition and skin-related biological activity. The findings suggest that witches\u2019 broom contains bioactive compounds influencing cell viability, migration, and inflammation, supporting its potential relevance in dermatological research and ethnopharmacology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1824563","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:22:28Z","timestamp":1782361348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From traditional remedy to in vitro evidence: phytochemical composition and skin-related pharmacological activity of birch witches\u2019 broom (Taphrina betulina)"],"prefix":"10.3389","volume":"17","author":[{"given":"Adrian","family":"Strus","sequence":"first","affiliation":[{"name":"Student Scientific Association \u201cHerbarium\u201d, Department of Pharmaceutical Biology, Faculty of Pharmacy, Medical University of Warsaw","place":["Warsaw, Poland"]},{"name":"Department of Pharmaceutical Microbiology and Bioanalysis, Faculty of Pharmacy, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Skowro\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Faculty of Pharmacy, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Malarczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology and Bioanalysis, Faculty of Pharmacy, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Kirzyc","sequence":"additional","affiliation":[{"name":"MicrobiotaLab, Department of Pharmaceutical Microbiology and Bioanalysis, Faculty of Pharmacy, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub P.","family":"Piwowarski","sequence":"additional","affiliation":[{"name":"MicrobiotaLab, Department of Pharmaceutical Microbiology and Bioanalysis, Faculty of Pharmacy, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"R\u00f3wnicki","sequence":"additional","affiliation":[{"name":"MicrobiotaLab, Department of Pharmaceutical Microbiology and Bioanalysis, Faculty of Pharmacy, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3390\/biom13071105","article-title":"Pharmacological potential of betulin as a multitarget compound","volume":"13","author":"Adepoju","year":"2023","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4338","DOI":"10.3390\/molecules26144338","article-title":"ESI-MS\/MS analysis of phenolic compounds from Aeonium arboreum leaf extracts and evaluation of their antioxidant and antimicrobial activities","volume":"26","author":"Affes","year":"2021","journal-title":"Molecules"},{"key":"B49","doi-asserted-by":"publisher","first-page":"721","DOI":"10.3390\/antiox10050721","article-title":"Comprehensive profiling of most widely used spices for their phenolic compounds through LC-ESI-QTOF-MS2 and their antioxidant potential","volume":"10","author":"Ali","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e00944","DOI":"10.1002\/mbo3.944","article-title":"Antimicrobial activity and chemical composition of white birch (Betula papyrifera marshall) bark extracts","volume":"9","author":"Blondeau","year":"2020","journal-title":"MicrobiologyOpen"},{"key":"B44","doi-asserted-by":"publisher","first-page":"20382","DOI":"10.3390\/ijms151120382","article-title":"Pine bark and green tea concentrated extracts: antioxidant activity and comprehensive characterization of bioactive compounds by HPLC\u2013ESI-QTOF-MS","volume":"15","author":"C\u00e1diz-Gurrea","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"11569","DOI":"10.3390\/ijms231911569","article-title":"A comprehensive review on beneficial effects of catechins on secondary mitochondrial diseases","volume":"23","author":"Chen","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e12709","DOI":"10.1111\/efp.12709","article-title":"Genetic resistance and tumour morphology in birch infected with Taphrina betulina","volume":"51","author":"Christita","year":"2021","journal-title":"For. Pathol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3549","DOI":"10.1111\/1462-2920.16037","article-title":"Distinct Taphrina strains from the phyllosphere of birch exhibiting a range of witches\u2019 broom disease symptoms","volume":"24","author":"Christita","year":"2022","journal-title":"Environ. Microbiol."},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-443-18694-3.00003-1","article-title":"Chapter 5 - Witches\u2019 broom disease of birch","volume-title":"Forest microbiology","author":"Christita","year":"2023"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7435621","DOI":"10.1155\/2017\/7435621","article-title":"HaCaT cells as a reliable in vitro differentiation model to dissect the Inflammatory\/repair response of human keratinocytes","volume":"2017","author":"Colombo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"B9","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ijantimicag.2011.02.014","article-title":"Recent advances in understanding the antibacterial properties of flavonoids","volume":"38","author":"Cushnie","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B10","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1353\/scd.2011.0030","article-title":"\u201cThe same nature as the reindeer\u201d: Johan Turi\u2019s portrayal of S\u00e1mi knowledge","volume":"83","author":"Dubois","year":"2011","journal-title":"Scand. Stud."},{"key":"B11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/1746-4269-9-57","article-title":"Johan Turi\u2019s animal, mineral, vegetable cures and healing practices: an in-depth analysis of Sami (saami) folk healing one hundred years ago","volume":"9","author":"Dubois","year":"2013","journal-title":"J. Ethnobiol. Ethnomed"},{"key":"B48","doi-asserted-by":"publisher","first-page":"114554","DOI":"10.1016\/j.jpba.2021.114554","article-title":"Isolation and quantification of diarylheptanoids from european hornbeam (Carpinus betulus L.) and HPLC-ESI-MS\/MS characterization of its antioxidative phenolics","volume":"210","author":"Felegyi-T\u00f3th","year":"2022","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B12","doi-asserted-by":"publisher","first-page":"593","DOI":"10.3390\/ph17050593","article-title":"Cistus, acacia, and lemon verbena valorization through response surface methodology: optimization studies and potential application in the pharmaceutical and nutraceutical industries","volume":"17","author":"Fernandes","year":"2024","journal-title":"Pharmaceuticals"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1016\/j.phytochem.2004.09.005","article-title":"Protein phosphorylation in Nicotiana tabacum cells in response to perception of lipopolysaccharides from Burkholderia cepacia","volume":"65","author":"Gerber","year":"2004","journal-title":"Phytochemistry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1177\/0022034509359125","article-title":"Factors affecting wound healing","volume":"89","author":"Guo","year":"2010","journal-title":"J. Dent. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.indcrop.2015.03.022","article-title":"Phenolic screening by HPLC\u2013DAD\u2013ESI\/MSn and antioxidant capacity of leaves, flowers and berries of Rubus grandifolius Lowe","volume":"73","author":"Gouveia-Figueira","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25194553","article-title":"Anti-cancer effects of green tea Epigallocatchin-3-Gallate and coffee chlorogenic acid","volume":"25","author":"Hayakawa","year":"2020","journal-title":"Molecules"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.1002\/9781118930717","volume-title":"Ethnopharmacology: a short history of a multidisciplinary field of research","author":"Heinrich","year":"2015"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2","DOI":"10.20450\/mjcce.2010.165","article-title":"HPLC-DAD-ESI-MSn identification of phenolic compounds in cultivated strawberries from macedonia","volume":"29","author":"Kajd\u017eanoska","year":"2010","journal-title":"Maced. J. Chem. Chem. Eng."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.3390\/molecules21091157","article-title":"Identification of iridoids in edible honeysuckle berries (Lonicera caerulea L. Var. kamtschatica sevast.) by UPLC-ESI-qTOF-MS\/MS","volume":"21","author":"Kucharska","year":"2016","journal-title":"Molecules"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1016\/j.phymed.2012.09.012","article-title":"Cognition-enhancing and neuroprotective activities of the standardized extract of Betula platyphylla bark and its major diarylheptanoids","volume":"19","author":"Lee","year":"2012","journal-title":"Phytomedicine"},{"key":"B19","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nprot.2007.30","article-title":"In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro","volume":"2","author":"Liang","year":"2007","journal-title":"Nat. Protoc."},{"key":"B20","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.phytochem.2012.01.008","article-title":"Procyanidin xylosides from the bark of Betula pendula","volume":"76","author":"Liimatainen","year":"2012","journal-title":"Phytochemistry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1924993","DOI":"10.1080\/22423982.2021.1924993","article-title":"S\u00e1mi traditional medicine: practices, usage, benefit, accessibility and relation to conventional medicine, a scoping review study","volume":"80","author":"Liu-Helmersson","year":"2021","journal-title":"Int. J. Circumpolar Health"},{"key":"B22","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.indcrop.2015.02.014","article-title":"HPLC-ESI-MSn characterization of phenolic compounds, terpenoid saponins, and other minor compounds in Bituminaria bituminosa","volume":"69","author":"Llorent-Mart\u00ednez","year":"2015","journal-title":"Industrial Crops Prod."},{"key":"B23","doi-asserted-by":"publisher","first-page":"14966","DOI":"10.1038\/s41598-019-51241-6","article-title":"Designing and optimization of an electrochemical substitute for the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay","volume":"9","author":"Mazloum-Ardakani","year":"2019","journal-title":"Sci. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2222908","DOI":"10.1080\/22423982.2023.2222908","article-title":"S\u00e1mi traditional medicine and complementary and alternative medicine - a descriptive study of use within the S\u00e1mi population of Sweden","volume":"82","author":"Ouma","year":"2023","journal-title":"Int. J. Circumpolar Health"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4060","DOI":"10.3390\/molecules27134060","article-title":"From traditional ethnopharmacology to modern natural drug discovery: a methodology discussion and specific examples","volume":"27","author":"Pirintsos","year":"2022","journal-title":"Molecules"},{"key":"B26","doi-asserted-by":"publisher","first-page":"114481","DOI":"10.1016\/j.foodres.2024.114481","article-title":"Evaluating birch leaf tea as a functional herbal beverage: beneficial impact on the urinary tract, and metabolism in human organism","volume":"189","author":"Popowski","year":"2024","journal-title":"Food Res. Int."},{"key":"B43","doi-asserted-by":"publisher","first-page":"5673","DOI":"10.3390\/molecules27175673","article-title":"Quantification of arbutin in cosmetics, drugs and food supplements by hydrophilic-interaction chromatography","volume":"27","author":"Repert","year":"2022","journal-title":"Molecules"},{"key":"B27","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.xphs.2024.12.007","article-title":"Natural drugs: trends, properties, and decline in FDA approvals","volume":"114","author":"Rose","year":"2025","journal-title":"J. Pharm. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/pr9050853","article-title":"Impact of environmental conditions on growth and the phenolic profile of Achillea atrata L","volume":"9","author":"Salomon","year":"2021","journal-title":"Processes"},{"key":"B29","doi-asserted-by":"publisher","first-page":"209","DOI":"10.4103\/0974-8490.182919","article-title":"Evaluating the anticancer potential of ethanolic gall extract of Terminalia chebula","volume":"8","author":"Shankara","year":"2016","journal-title":"(Gaertn.) retz. (Combretaceae)."},{"key":"B30","doi-asserted-by":"publisher","first-page":"12507","DOI":"10.3390\/ijms232012507","article-title":"Betula Alba bark extract and Empetrum nigrum fruit juice, a natural alternative to niacinamide for skin barrier benefits","volume":"23","author":"Smiljanic","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.chroma.2005.06.042","article-title":"Isolation and structure elucidation of phenolic compounds from longan (Dimocarpus longan lour.) seed by high-performance liquid chromatography-electrospray ionization mass spectrometry","volume":"1085","author":"Soong","year":"2005","journal-title":"J. Chromatogr. A"},{"key":"B32","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12865-017-0202-3","article-title":"Poly I:C induces collective migration of HaCaT keratinocytes via IL-8","volume":"18","author":"Takada","year":"2017","journal-title":"BMC Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.3390\/jpm12091370","article-title":"Skin Inflammation-A cornerstone in dermatological conditions","volume":"12","author":"Tampa","year":"2022","journal-title":"J. Pers. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.3389\/fpls.2019.01441","article-title":"Accumulation of catechin and proanthocyanidins in black poplar stems after infection by plectosphaerella populi: hormonal regulation, biosynthesis and antifungal activity","volume":"10","author":"Ullah","year":"2019","journal-title":"Front. in Plant Sci."},{"key":"B35","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-61779-080-5_20","article-title":"Cell sensitivity assays: the MTT assay","volume-title":"Cancer cell culture: methods and protocols","author":"Van Meerloo","year":"2011"},{"key":"B36","doi-asserted-by":"publisher","first-page":"69","DOI":"10.21315\/tlsr2020.31.1.5","article-title":"Phytochemicals and cytotoxicity of Quercus infectoria ethyl acetate extracts on human cancer cells","volume":"31","author":"Wan Nur Suzilla Wan","year":"2020","journal-title":"Trop. Life Sci. Res."},{"key":"B37","volume-title":"WHO global report on traditional and complementary medicine 2019","author":"World Health","year":"2019"},{"key":"B38","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.foodchem.2018.09.120","article-title":"Profile of phenolic compounds and antioxidant activity of finger millet varieties","volume":"275","author":"Xiang","year":"2019","journal-title":"Food Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"112414","DOI":"10.1016\/j.jep.2019.112414","article-title":"The ethnopharmacological literature: an analysis of the scientific landscape","volume":"250","author":"Yeung","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.31557\/APJCP.2023.24.7.2383","article-title":"The selective cytotoxicity of Quercus brantii lindl. Galls on A375 and SK-MEL-3 human malignant melanoma cell lines","volume":"24","author":"Yosefsani","year":"2023","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"134471","DOI":"10.1016\/j.foodchem.2022.134471","article-title":"Profiling of naturally occurring proanthocyanidins and other phenolic compounds in a diverse peach germplasm by LC-MS\/MS","volume":"403","author":"Zhang","year":"2023","journal-title":"Food Chem."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1327164","article-title":"Characterization, antioxidant and antitumor activities of phenolic compounds from Amomum villosum Lour","volume":"11","author":"Zhang","year":"2024","journal-title":"Front. Nutr."},{"key":"B42","doi-asserted-by":"publisher","first-page":"22463","DOI":"10.3390\/molecules201219859","article-title":"Phenolic profiling of Duchesnea indica combining macroporous resin chromatography (MRC) with HPLC-ESI-MS\/MS and ESI-IT-MS","volume":"20","author":"Zhu","year":"2015","journal-title":"Molecules"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1824563\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:22:30Z","timestamp":1782361350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1824563\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":49,"alternative-id":["10.3389\/fphar.2026.1824563"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1824563","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]},"article-number":"1824563"}}