{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T02:39:11Z","timestamp":1787279951998,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Plant Sci."],"abstract":"<jats:p>Willow bark is traditionally used for pharmaceutical purposes. Evaluation is so far based on the salicylate content, however, health promoting effects of extracts might be attributed to the interaction of those salicylates with other compounds, which support and complement their action. So far, only <jats:italic>S. purpurea<\/jats:italic>, <jats:italic>S. daphnoides<\/jats:italic>, and <jats:italic>S. fragilis<\/jats:italic> are included in pharmaceutical extracts. Crossing with other species could result in a more diverse secondary metabolite profile with higher pharmacological value. With the help of targeted inter- and intraspecific crossing, new chemotypes were generated, whereby nine different <jats:italic>Salix<\/jats:italic> genotypes (<jats:italic>S. alba<\/jats:italic>, <jats:italic>S. daphnoides<\/jats:italic>, <jats:italic>S. humboldtiana<\/jats:italic>, <jats:italic>S. lasiandra<\/jats:italic>, <jats:italic>S. nigra<\/jats:italic>, <jats:italic>S. pentandra<\/jats:italic>, <jats:italic>S. purpurea<\/jats:italic>, <jats:italic>S. x rubens<\/jats:italic>, <jats:italic>S. viminalis<\/jats:italic>) were included in the study. Based on substances known for their health promoting potential and characteristic for <jats:italic>Salix<\/jats:italic> (selected phenolic compounds including salicylates), a targeted metabolomics analysis and clustering of 92 generated <jats:italic>Salix<\/jats:italic> clones was performed revealing four different cluster\/chemoprofiles. In more specific, one group is formed by <jats:italic>S. daphnoides<\/jats:italic> clones and inter- and intraspecific hybrids, a second group by <jats:italic>S. viminalis<\/jats:italic> clones and inter- and intraspecific hybrids, a third group generally formed by <jats:italic>S. alba<\/jats:italic>, <jats:italic>S. pentandra<\/jats:italic>, <jats:italic>S. x rubens<\/jats:italic>, and <jats:italic>S. lasiandra<\/jats:italic> clones and hybrids, and a fourth group by <jats:italic>S. purpurea<\/jats:italic> clones and inter- and intraspecific hybrids. Clustering on the basis of the selected phenolic compounds can be used for identifying <jats:italic>Salix<\/jats:italic> clones with a different compound profile. New combinations of secondary plant metabolites offer the chance to identify <jats:italic>Salix<\/jats:italic> crosses with improved effects on human health.<\/jats:p>","DOI":"10.3389\/fpls.2021.579820","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:42:06Z","timestamp":1617262926000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Chemoprofiling as Breeding Tool for Pharmaceutical Use of Salix"],"prefix":"10.3389","volume":"12","author":[{"given":"Nadja","family":"F\u00f6rster","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriaki","family":"Antoniadou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Zander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Baur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena Karolin","family":"Mittermeier-Kle\u00dfinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Dawid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ulrichs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Mewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1007\/s00044-011-9746-6","article-title":"Synthesis and biological evaluation of novel series of chalcone derivatives as inhibitors of cyclooxygenase and LPS-induced TNF-\u03b1 with potent antioxidant properties.","volume":"21","author":"Bandgar","year":"2012","journal-title":"Med. Chem. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.phymed.2008.07.010","article-title":"Willow bark extract (Salicis cortex) for gonarthrosis and coxarthrosis \u2013 Results of a cohort study with a control group.","volume":"15","author":"Beer","year":"2008","journal-title":"Phytomedicine"},{"key":"B3","first-page":"53","article-title":"Breeding of multipurpose willows on the basis of Salix daphnoides Vill., Salix purpurea L. and Salix viminalis L.","volume":"68","author":"Bubner","year":"2018","journal-title":"Landbauforschung"},{"key":"B4","author":"Carlson","year":"2018","journal-title":"The Genomic Basis of Heterosis in High-Yielding Triploid Hybrids of Willow (Salix spp.) Bioenergy Crops."},{"key":"B5","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s11101-010-9194-9","article-title":"The effect of hybridization on secondary metabolites and herbivore resistance: implications for the evolution of chemical diversity in plants.","volume":"10","author":"Cheng","year":"2011","journal-title":"Phytochem. Rev."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2016.00057","article-title":"The gastrointestinal tract as a key target organ for the health-promoting effects of dietary proanthocyanidins.","volume":"3","author":"Cires","year":"2017","journal-title":"Front. Nutr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/s10681-013-0981-4","article-title":"Genetic combining ability and heterosis for important vitamins and antioxidant pigments in cauliflower (Brassica oleracea var. botrytis L.).","volume":"195","author":"Dey","year":"2014","journal-title":"Euphytica"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/386953","article-title":"The study of interactions between active compounds of coffee and willow (Salix sp.) bark water extract.","volume":"2014","author":"Durak","year":"2014","journal-title":"Biomed Res. Int."},{"key":"B9","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1080\/01635581.2014.936949","article-title":"The ethanolic extract of bark from Salix aegyptiaca L. inhibits the metastatic potential and epithelial to mesenchymal transition of colon cancer cell lines.","volume":"66","author":"Enayat","year":"2014","journal-title":"Nutr. Cancer"},{"key":"B10","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1080\/01635581.2013.850966","article-title":"Anticarcinogenic effects of the ethanolic extract of Salix aegyptiaca in colon cancer cells: involvement of Akt\/PKB and MAPK pathways.","volume":"65","author":"Enayat","year":"2013","journal-title":"Nutr. Cancer"},{"key":"B11","year":"2017","journal-title":"Salicis Cortex - Willow bark."},{"key":"B12","first-page":"353","article-title":"Trease and Evans\u2019 Pharmacognosy, 15th Edition.","volume":"149","author":"Evans","year":"2000","journal-title":"Int. J. Appl. Biol. Pharm."},{"key":"B13","article-title":"Eignung unterschiedlicher salicylathaltiger Salix-Klone f\u00fcr die arzneimittelindustrie","author":"F\u00f6rster","year":"2010","journal-title":"Berliner \u00d6kophysiologische und Phytomedizinische Schriften"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4660","DOI":"10.1039\/c6fo01231k","article-title":"Characteristic single glucosinolates from Moringa oleifera: induction of detoxifying enzymes and lack of genotoxic activity in various model systems.","volume":"7","author":"F\u00f6rster","year":"2016","journal-title":"Food Funct."},{"key":"B15","first-page":"99","article-title":"Influence of the season on the salicylate and phenolic glycoside contents in the bark of Salix daphnoides, Salix pentandra, and Salic purpurea.","volume":"82","author":"F\u00f6rster","year":"2008","journal-title":"J. Appl. Bot. Food Qual."},{"key":"B16","first-page":"505","article-title":"The pharmacological potential of catechin.","volume":"57","author":"Ganeshpurkar","year":"2020","journal-title":"Indian J. Biochem. Biophys."},{"key":"B17","first-page":"35","article-title":"Investigating the synergistic antioxidant effects of some flavonoid and phenolic compounds.","volume":"1","author":"Hajimehdipoor","year":"2014","journal-title":"Res. J. Pharmacogn."},{"key":"B18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1034\/j.1399-3054.1998.1020114.x","article-title":"Nitrogen-induced reduction in leaf phenolic level is not accompanied by increased rust frequency in a compatible willow (Salix myrsinifolia)-Melampsora rust infection.","volume":"102","author":"Hakulinen","year":"1998","journal-title":"Physiol. Plant."},{"key":"B19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1046\/j.1439-0329.2000.00184.x","article-title":"Variation in leaf phenolics of field-cultivated willow (Salix myrsinifolia) clones in relation to occurrence of Melampsora rust.","volume":"30","author":"Hakulinen","year":"2000","journal-title":"Eur J Plant Pathol"},{"key":"B20","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1023\/A:1023829506473","article-title":"Inheritance patterns of phenolics in F1, F2, and back-cross hybrids of willows: implications for herbivore responses to hybrid plants.","volume":"29","author":"Hallgren","year":"2003","journal-title":"J. Chem. Ecol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1016\/j.freeradbiomed.2012.12.006","article-title":"Willow bark extract increases antioxidant enzymes and reduces oxidative stress through activation of Nrf2 in vascular endothelial cells and Caenorhabditis elegans.","volume":"65","author":"Ishikado","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"B22","first-page":"231","article-title":"Flavan-3-ols and procyanidins from the bark of Salix purpurea.","volume":"62","author":"J\u00fcrgenliemk","year":"2007","journal-title":"Pharmazie"},{"key":"B23","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1002\/pca.873","article-title":"HPLC-MS\/MS analysis of willow bark extracts contained in pharmaceutical preparations.","volume":"16","author":"Kammerer","year":"2005","journal-title":"Phytochem. Anal."},{"key":"B24","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1055\/s-0031-1296917","article-title":"Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract.","volume":"55","author":"Khayyal","year":"2005","journal-title":"Arzneimittelforschung"},{"key":"B25","first-page":"S69","article-title":"The anti-inflammatory, antipyretic and analgesic effect of willow bark extract, STW-I, cannot be explained solely on the basis of its salicin content.","volume":"11","author":"Khayyal","year":"2003","journal-title":"Osteoarthritis Cartilage"},{"key":"B26","article-title":"Untersuchungen zur Phenolglykosidkonzentration ausgew\u00e4hlter intra- und interspezifischer Kreuzungen salicinreicher Biomasseweiden","author":"K\u00f6hler","year":"2016","journal-title":"Berliner \u00d6kophysiologische und Phytomedizinische Schriften"},{"key":"B27","first-page":"275","article-title":"Wirksamkeit und Vertr\u00e4glichkeit eines w\u00e4ssrig ausgezogenen Weidenrindenextraktes bei Patienten mit H\u00fcft- und Kniearthrose.","volume":"25","author":"Lardos","year":"2004","journal-title":"Z. Phytother."},{"key":"B28","first-page":"1155","article-title":"Synthesis and in vitro cytotoxic activity of novel chalcone-like agents.","volume":"16","author":"Letafat","year":"2013","journal-title":"Iran. J. Basic Med. Sci."},{"key":"B29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/ajcn\/78.3.517S","article-title":"Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals.","volume":"78","author":"Liu","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.indcrop.2016.09.042","article-title":"A new approach to discriminate Rosmarinus officinalis L. plants with antioxidant activity based on HPTLC fingerprint and targeted phenolic analysis combined with PCA.","volume":"94","author":"Maldini","year":"2016","journal-title":"Ind. Crop Prod."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4103\/2152-7806.73804","article-title":"Natural anti-inflammatory agents for pain relief.","volume":"1","author":"Maroon","year":"2010","journal-title":"Surg. Neurol. Int."},{"key":"B32","first-page":"2401","article-title":"Salicylate in Arzneimitteln.","volume":"127","author":"Meier","year":"1987","journal-title":"DAZ"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1002\/ece3.1923","article-title":"Female Salix viminalis are more severely infected by Melampsora spp. but neither sex experiences associational effects.","volume":"6","author":"Moritz","year":"2016","journal-title":"Ecol. Evol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/s10354-007-0437-3","article-title":"Willow bark extract: the contribution of polyphenols to the overall effect.","volume":"157","author":"Nahrstedt","year":"2007","journal-title":"Wien. Med. Wochenschr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.biopha.2017.10.064","article-title":"Chlorogenic acid (CGA): a pharmacological review and cell for further research.","volume":"97","author":"Naveed","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.foreco.2014.01.016","article-title":"Variable patterns of inheritance of ecologically important plants secondary metabolites in an inter-specific eucalypt hybrid.","volume":"318","author":"O\u2019Reilly-Wapstra","year":"2014","journal-title":"Forest Ecol. Manag."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.2307\/2656824","article-title":"The effects of hybridization in plants on secondary chemistry: implications for the ecology and evolution of plant-herbivore interactions.","volume":"87","author":"Orians","year":"2000","journal-title":"Am. J. Bot."},{"key":"B38","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/s0305-1978(99)00101-5","article-title":"Phenolic glycosides and condensed tannins in Salix sericea, S. eriocephala and their F1 hybrids: not all hybrids are created equal.","volume":"28","author":"Orians","year":"2000","journal-title":"Biochem. Syst. Ecol."},{"key":"B39","doi-asserted-by":"crossref","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: an overview.","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/biom10101391","article-title":"Identification and accumulation of phenolic compounds in the leaves and bark of Salix alba (L.) and their biological potential.","volume":"10","author":"Piatczak","year":"2020","journal-title":"Biomolecules"},{"key":"B41","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1080\/07352689309701902","article-title":"What can molecular and morphological markers tell us about plant hybridization.","volume":"12","author":"Rieseberg","year":"1993","journal-title":"Crit. Rev. Plant Sci."},{"key":"B42","first-page":"759","article-title":"Heterosis and heterobeltiosis for morpho-physical, phenolics, flavonoids and antioxidants in grape (Vitis vinifera) hybrids.","volume":"87","author":"Sahoo","year":"2017","journal-title":"Indian J. Agric. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.ijpharm.2010.09.035","article-title":"In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid.","volume":"403","author":"Sato","year":"2011","journal-title":"Int. J. Pharm."},{"key":"B44","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s002280100325","article-title":"Pharmacokinetics of salicin after oral administration of a standardised willow bark extract.","volume":"57","author":"Schmid","year":"2001","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B45","author":"Shao","year":"1991","journal-title":"Phytochemischer Atlas der Schweizer Weiden."},{"key":"B46","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.fitote.2017.03.005","article-title":"Variations in the chemical composition and content of salicylic glycosides in the bark of Salix purpurea from natural locations in their significance for breeding.","volume":"118","author":"Sulima","year":"2017","journal-title":"Fitoterapia"},{"key":"B47","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/b978-0-12-813820-5.00031-3","article-title":"Chapter 31 \u2013 Purple willow (Salix purpurea L.) and its potential uses for the treatment of arthritis and rheumatism","author":"Sulima","year":"2019","journal-title":"Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases"},{"key":"B48","first-page":"208","article-title":"Drug development from natural products: exploiting synergistic effects.","volume":"48","author":"Ulrich-Merzenich","year":"2010","journal-title":"Indian J. Exp. Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1007\/s11418-007-0223-y","article-title":"Anticarcinogenic compounds in the Uzbek medicinal plant, Helichrysum maracandicum.","volume":"62","author":"Yagura","year":"2008","journal-title":"J. Nat. Med."}],"container-title":["Frontiers in Plant Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2021.579820\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:42:30Z","timestamp":1617262950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2021.579820\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":49,"alternative-id":["10.3389\/fpls.2021.579820"],"URL":"https:\/\/doi.org\/10.3389\/fpls.2021.579820","relation":{},"ISSN":["1664-462X"],"issn-type":[{"value":"1664-462X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,1]]},"article-number":"579820"}}