{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:21:42Z","timestamp":1790882502214,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Klosterfrau Vertriebsgesellschaft mbH, Germany","award":["3550084100"],"award-info":[{"award-number":["3550084100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Extracts from Drosera rotundifolia are traditionally used to treat cough symptoms during a common cold. The present study aimed to investigate the impact of extracts from D. rotundifolia and active compounds on the respiratory tract. Tracheal slices of C57BL\/6N mice were used ex vivo to examine effects on airway smooth muscle (ASM) and ciliary beat frequency (CBF). Phosphodiesterase (PDE) inhibition assays were carried out to test whether PDE1 or PDE4 are targeted by the active compounds. An ethanol\u2013water extract, as well as an aqueous fraction of this extract, exerted antispasmodic properties against acetylcholine-induced contractions. In addition, contractions induced by 60 mM K+ were abrogated by the aqueous fraction. Effects on ASM could be attributed to the flavonoids quercetin, 2\u2033-O-galloylhyperoside and hyperoside. Moreover, the Drosera extract and the aqueous fraction increased the CBF of murine tracheal slices. Quercetin and 2\u2033-O-galloylhyperoside were identified as active compounds involved in the elevation of CBF. Both compounds inhibited PDE1A and PDE4D. The elevation of CBF was mimicked by the subtype-selective PDE inhibitor rolipram (PDE4) and by 8-methoxymethyl-IBMX. In summary, our study shows, for the first time, that a Drosera extract and its flavonoid compounds increase the CBF of murine airways while antispasmodic effects were transferred to ASM.<\/jats:p>","DOI":"10.3390\/molecules27196622","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T23:31:43Z","timestamp":1665358303000},"page":"6622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of Extracts and Flavonoids from Drosera rotundifolia L. on Ciliary Beat Frequency and Murine Airway Smooth Muscle"],"prefix":"10.3390","volume":"27","author":[{"given":"Alexander","family":"Hake","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry\u2014Pharmacology, University of M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Institute of Pharmaceutical Biology and Phytochemistry, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Begrow","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry\u2014Pharmacology, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7437-8151","authenticated-orcid":false,"given":"Verena","family":"Spiegler","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Phytochemistry, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Symma","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Phytochemistry, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-8384","authenticated-orcid":false,"given":"Andreas","family":"Hensel","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Phytochemistry, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"D\u00fcfer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry\u2014Pharmacology, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Biology, ecology, use, conservation and cultivation of round-leaved sundew (Drosera rotundifolia L.): A review","volume":"18","author":"Baranyai","year":"2016","journal-title":"Mires Peat"},{"key":"ref_2","unstructured":"Council of Europe (2020). Methods of Preparation of Homeopathic Stocks and Potentisation, Council of Europe. European Pharmacopoiea 10th Ed."},{"key":"ref_3","unstructured":"(2011). Hom\u00f6opathisches Arzneibuch: Monographie Drosera, Deutscher Apotheker Verlag."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1007\/s00216-011-4690-3","article-title":"Identification and quantification of flavonoids and ellagic acid derivatives in therapeutically important Drosera species by LC-DAD, LC-NMR, NMR, and LC-MS","volume":"400","author":"Zehl","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.phytochem.2015.08.017","article-title":"Flavonoids as chemotaxonomic markers in the genus Drosera","volume":"118","author":"Braunberger","year":"2015","journal-title":"Phytochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1002\/cbdv.201200359","article-title":"Phytochemistry of the carnivorous sundew genus Drosera (Droseraceae)\u2014Future perspectives and ethnopharmacological relevance","volume":"10","author":"Egan","year":"2013","journal-title":"Chem. Biodivers."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tienaho, J., Reshamwala, D., Karonen, M., Silvan, N., Korpela, L., Marjom\u00e4ki, V., and Sarjala, T. (2021). Field-Grown in vitro propagated round-leaved Sundew (Drosera rotundifolia L.) show differences in metabolic profiles and biological activities. Molecules, 26.","DOI":"10.3390\/molecules26123581"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1078\/0944-7113-00031","article-title":"Anti-inflammatory and spasmolytic activity of extracts from Droserae herba","volume":"8","author":"Melzig","year":"2001","journal-title":"Phytomedicine"},{"key":"ref_9","first-page":"402","article-title":"In vitro antispasmodic and anti-inflammatory effects of Drosera rotundifolia","volume":"54","author":"Krenn","year":"2004","journal-title":"Arzneimittelforschung"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1055\/s-2007-971689","article-title":"Pharmacological and chemical investigation of thyme liquid extracts","volume":"41","author":"Lemli","year":"1981","journal-title":"Planta Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/ptr.1666","article-title":"Comparison of the antiinflammatory effects of Drosera rotundifolia and Drosera madagascariensis in the HET-CAM assay","volume":"19","author":"Paper","year":"2005","journal-title":"Phytother. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jep.2009.06.009","article-title":"Drosera rotundifolia and Drosera tokaiensis suppress the activation of HMC-1 human mast cells","volume":"125","author":"Fukushima","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0378-8741(97)00129-3","article-title":"Antimicrobial activity of aerial parts of Drosera peltata Smith on oral bacteria","volume":"60","author":"Didry","year":"1998","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1038\/s41598-021-81843-y","article-title":"Low-dose Drosera rotundifolia induces gene expression changes in 16HBE human bronchial epithelial cells","volume":"11","author":"Bellavite","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"a028241","DOI":"10.1101\/cshperspect.a028241","article-title":"Cilia and mucociliary clearance","volume":"9","author":"Ostrowski","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1159\/000338505","article-title":"Procaterol-stimulated increases in ciliary bend amplitude and ciliary beat frequency in mouse bronchioles","volume":"29","author":"Daikokua","year":"2012","journal-title":"J. Cell. Physiol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3389\/fphar.2020.00609","article-title":"Respiratory cilia as a therapeutic target of phosphodiesterase inhibitors","volume":"11","author":"Joskova","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1152\/jappl.1990.68.4.1421","article-title":"Mucociliary interaction in vitro: Effects of physiological and inflammatory stimuli","volume":"68","author":"Seybold","year":"1990","journal-title":"J. Appl. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s12325-012-0014-z","article-title":"Effect of myrtol standardized and other substances on the respiratory tract: Ciliary beat frequency and mucociliary clearance as parameters","volume":"29","author":"Begrow","year":"2012","journal-title":"Adv. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1111\/j.1476-5381.2012.01929.x","article-title":"Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro","volume":"166","author":"Milara","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/ardp.19662990705","article-title":"Flavonoide aus Drosera rotundifolia L.","volume":"299","author":"Bienenfeld","year":"1966","journal-title":"Arch. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1111\/j.1476-5381.1992.tb14451.x","article-title":"Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: Biochemical and pharmacological analysis using selective inhibitors","volume":"106","author":"Philpott","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/sj.bjp.0702779","article-title":"Anti-spasmogenic activity of isoenzyme-selective phosphodiesterase inhibitors in guinea-pig trachealis","volume":"128","author":"Bernareggi","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1096\/fj.03-0274com","article-title":"PDE4D plays a critical role in the control of airway smooth muscle contraction","volume":"17","author":"Jin","year":"2003","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1111\/j.1476-5381.1996.tb15653.x","article-title":"The effect of isoenzyme-selective PDE inhibitors on methacholine-induced contraction of guineapig and rat ileum","volume":"118","author":"Tomkinson","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_26","first-page":"201","article-title":"Main constituents of a commercial Drosera fluid extract and their antagonist activity at muscarinic M3 receptors in guinea-pig ileum","volume":"57","author":"Koloziej","year":"2002","journal-title":"Pharmazie"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0944-7113(96)80038-9","article-title":"Antispasmodic effects of hydroalcoholic extract of Marrubium vulgare on isolated tissues","volume":"3","author":"Schlemper","year":"1996","journal-title":"Phytomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1080\/10826079808001264","article-title":"Determination of Naphthoquinones in Droserae herba by Reversed-Phase High Performance Liquid Chromatography","volume":"21","author":"Krenn","year":"1998","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/157341209787314936","article-title":"Noteworthy Secondary Metabolites Naphthoquinones\u2014Their Occurrence, Pharmacological Properties and Analysis","volume":"5","author":"Babula","year":"2009","journal-title":"CPA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0165-1218(83)90182-9","article-title":"Mutagenicity of natural naphthoquinones and benzoquinones in the Salmonella\/microsome test","volume":"124","author":"Tikkanen","year":"1983","journal-title":"Mutat. Res. Genet. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1152\/ajplung.00125.2013","article-title":"Quercetin acutely relaxes airway smooth muscle and potentiates \u03b2-agonist-induced relaxation via dual phosphodiesterase inhibition of PLC\u03b2 and PDE4","volume":"305","author":"Townsend","year":"2013","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cbi.2019.02.029","article-title":"2\u2032O-galloylhyperin attenuates LPS-induced acute lung injury via up-regulation antioxidation and inhibition of inflammatory responses in vivo","volume":"304","author":"Zhang","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3109\/13880209.2010.494307","article-title":"Pharmacological studies on Hypericum perforatum fractions and constituents","volume":"49","author":"Khan","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1016\/j.bcp.2004.06.030","article-title":"Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships","volume":"68","author":"Ko","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0024-3205(94)00787-X","article-title":"Effects of naturally occuring flavonoids on mitogen-induced lymphocyte proliferation and mixed lymphocyte culture","volume":"54","author":"Nmngoong","year":"1993","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s00424-017-1988-9","article-title":"A low Ca2+i -induced enhancement of cAMP-activated ciliary beating by PDE1A inhibition in mouse airway cilia","volume":"469","author":"Kogiso","year":"2017","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1113\/EP086681","article-title":"Ca2+i modulation of cAMP-stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice","volume":"103","author":"Kogiso","year":"2018","journal-title":"Exp. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2500\/ajra.2011.25.3643","article-title":"Quercetin increases cystic fibrosis transmembrane conductance regulator\u2013mediated chloride transport and ciliary beat frequency: Therapeutic implications for chronic rhinosinusitis","volume":"25","author":"Zhang","year":"2011","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1017\/S000711451000053X","article-title":"Oral bioavailability of quercetin from different quercetin glycosides in dogs","volume":"104","author":"Reinboth","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1055\/s-0031-1298374","article-title":"Effect of silymarin and harpagoside on inflammation reaction of BEAS-2B cells, on ciliary beat frequency (CBF) of trachea explants and on mucociliary clearance (MCC)","volume":"78","author":"Boeckenholt","year":"2012","journal-title":"Planta Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1046\/j.1365-2818.2003.01209.x","article-title":"All-digital image capture and whole-field analysis of ciliary beat frequency","volume":"211","author":"Sisson","year":"2003","journal-title":"J. Microsc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1165\/rcmb.2005-0417OC","article-title":"Ciliary beat frequency is maintained at a maximal rate in the small airways of mouse lung slices","volume":"35","author":"Delmotte","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:47:03Z","timestamp":1760143623000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":42,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27196622"],"URL":"https:\/\/doi.org\/10.3390\/molecules27196622","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]}}}