{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:00:35Z","timestamp":1789002035646,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T00:00:00Z","timestamp":1565308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There is currently much interest in finding new phytochemicals among plants and fungi as nature-based alternatives to replace problematic herbicides such as glyphosate, which are preferentially used in agricultural production. We discovered striking herbicidal potency in Cordyceps militaris (L.) and identified cordycepin as its principal plant growth inhibitor. Cordycepin obtained as an ethyl acetate extract was subjected to column chromatography and evaluated for its bioassay-guided phytotoxic capacity against Raphanus sativus (radish), showing a maximum inhibition on germination and growth of radish (IC50 = 0.052\u20130.078 mg\/mL). Gas chromatography-mass spectrometry (GC-MS) (m\/z: 251.2) and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) ([M + Na]+ m\/z: 274.1; [M + H]+ m\/z: 252.1) analyses confirmed cordycepin as the major component of the tested column fraction (55.38%). At 0.04 mg\/mL, cordycepin showed 3.8\u20135.9- and 3.3\u20133.7-fold greater inhibition of the germination and growth of radish than benzoic acid (BA) and glyphosate, respectively. Compared with BA, isolated cordycepin reduced plant chlorophyll and carotenoid contents (2.0\u20139.5 -fold), while proline, total phenolic and total flavonoid contents were increased 1.2\u20131.8-fold. Finally, cordycepin promoted electrolyte leakage and malondialdehyde accumulation in radish aerial parts. Thus, cordycepin successfully isolated from Cordyceps militaris is a highly potent plant growth inhibitor with pending worldwide patent and may become a potential plant-based novel alternative to the disputed glyphosate.<\/jats:p>","DOI":"10.3390\/molecules24162901","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T11:11:31Z","timestamp":1565349091000},"page":"2901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Cordycepin Isolated from Cordyceps militaris: Its Newly Discovered Herbicidal Property and Potential Plant-Based Novel Alternative to Glyphosate"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9545-5929","authenticated-orcid":false,"given":"Tran Ngoc","family":"Quy","sequence":"first","affiliation":[{"name":"Graduate School for International Development and Cooperation, Hiroshima University, Hiroshima 739-8529, Japan"},{"name":"Can Tho University, Can Tho City 902070, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-5698","authenticated-orcid":false,"given":"Tran Dang","family":"Xuan","sequence":"additional","affiliation":[{"name":"Graduate School for International Development and Cooperation, Hiroshima University, Hiroshima 739-8529, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-301X","authenticated-orcid":false,"given":"Yusuf","family":"Andriana","sequence":"additional","affiliation":[{"name":"Graduate School for International Development and Cooperation, Hiroshima University, Hiroshima 739-8529, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3563-2887","authenticated-orcid":false,"given":"Hoang-Dung","family":"Tran","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology, Nguyen Tat Thanh University, 298A-300A Nguyen Tat Thanh Street, Ward 13, District 4, Ho Chi Minh 72820, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-7121","authenticated-orcid":false,"given":"Tran Dang","family":"Khanh","sequence":"additional","affiliation":[{"name":"Agricultural Genetics Institute, Pham Van Dong Street, Hanoi 122000, Vietnam"},{"name":"Center for Expert, Vietnam National University of Agriculture, Hanoi 131000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8910-1200","authenticated-orcid":false,"given":"Rolf","family":"Teschke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, 63450 Hanau, Germany"},{"name":"Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt\/ Main, D-60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/j.1439-037X.2005.00170.x","article-title":"Decomposition of Allelopathic Plants in Soil","volume":"191","author":"Xuan","year":"2005","journal-title":"J. Agron. Crop. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/17429145.2016.1159342","article-title":"Allelopathy: Driving mechanisms governing its activity in agriculture","volume":"11","author":"Trezzi","year":"2016","journal-title":"J. Plant Interact."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.sajb.2014.04.014","article-title":"The impact of Tunisian Capparidaceae species on cytological, physiological and biochemical mechanisms in lettuce","volume":"93","author":"Ladhari","year":"2014","journal-title":"S. Afr. J. Bot."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.sajb.2014.04.009","article-title":"Physiological and biochemical mechanisms of allelochemicals in aqueous extracts of diploid and mixoploid Trigonella foenum-graecum L.","volume":"93","author":"Omezzine","year":"2014","journal-title":"S. Afr. J. Bot."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Osivand, A., Araya, H., Appiah, K.S., Mardani, H., Ishizaki, T., and Fujii, Y. (2018). Allelopathy of Wild Mushrooms\u2014An Important Factor for Assessing Forest Ecosystems in Japan. Forests, 9.","DOI":"10.3390\/f9120773"},{"key":"ref_6","first-page":"150","article-title":"Screening of some pathogenic fungi for their herbicidal potential against parthenium weed","volume":"20","author":"Idrees","year":"2008","journal-title":"Pak. J. Phytopathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1439-0434.2006.01129.x","article-title":"Characterization of a Phytotoxin from Phoma herbarum for Management of Parthenium hysterophorus L.","volume":"154","author":"Vikrant","year":"2006","journal-title":"J. Phytopathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"542","DOI":"10.2307\/1936497","article-title":"Influence of Naturally Occurring Compounds on Germination and Growth of Jack Pine","volume":"48","author":"Brown","year":"1967","journal-title":"Ecology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cropro.2004.08.004","article-title":"Biological control of weeds and plant pathogens in paddy rice by exploiting plant allelopathy: An overview","volume":"24","author":"Xuan","year":"2005","journal-title":"Crop. Prot."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1614\/WS-07-102.1","article-title":"Weed-Suppressing Potential of Dodder (Cuscuta hygrophilae) and its Phytotoxic Constituents","volume":"56","author":"Khanh","year":"2008","journal-title":"Weed Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/j.jff.2013.06.002","article-title":"Composition and characterization of cordyxanthins from Cordyceps militaris fruit bodies","volume":"5","author":"Dong","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1248\/bpb.26.691","article-title":"Antifatigue and Antistress Effect of the Hot-Water Fraction from Mycelia of Cordyceps sinensis","volume":"26","author":"Koh","year":"2003","journal-title":"Boil. Pharm. Bull."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.ijbiomac.2016.02.009","article-title":"Immunomodulatory and antioxidative activity of Cordyceps militaris polysaccharides in mice","volume":"86","author":"Liu","year":"2016","journal-title":"Int. J. Boil. Macromol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.bbrc.2018.02.188","article-title":"The inhibitory effect of Cordycepin on the proliferation of cisplatin-resistant A549 lung cancer cells","volume":"498","author":"Cho","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Quy, T.N., and Xuan, T.D. (2019). Xanthine Oxidase Inhibitory Potential, Antioxidant and Antibacterial Activities of Cordyceps militaris (L.) Link Fruiting Body. Medicines, 6.","DOI":"10.3390\/medicines6010020"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20808","DOI":"10.3390\/molecules191220808","article-title":"Optimization of Ultrasonic-Assisted Extraction of Cordycepin from Cordyceps militaris Using Orthogonal Experimental Design","volume":"19","author":"Wang","year":"2014","journal-title":"Molecules"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1007\/s10637-012-9859-x","article-title":"The nucleoside antagonist cordycepin causes DNA double strand breaks in breast cancer cells","volume":"30","author":"Lee","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00280-006-0354-y","article-title":"The apoptoic effect of cordycepin on human OEC-M1 oral cancer line","volume":"60","author":"Wu","year":"2007","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.scienta.2015.06.013","article-title":"Alleviation of allelopathic stress of benzoic acid by indole acetic acid in Solanum lycopersicum","volume":"192","author":"Sunaina","year":"2015","journal-title":"Sci. Hortic."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0261-2194(02)00242-9","article-title":"Inderjit Challenges and opportunities in implementing allelopathy for natural weed management","volume":"22","author":"Bhowmik","year":"2003","journal-title":"Crop Prot."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0305-1978(02)00150-3","article-title":"Effects of root exudates and aqueous root extracts of cucumber (Cucumis sativus) and allelochemicals, on photosynthesis and antioxidant enzymes in cucumber","volume":"31","author":"Yu","year":"2003","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plaphy.2018.04.037","article-title":"Comparative phytotoxicity of usnic acid, salicylic acid, cinnamic acid and benzoic acid on photosynthetic apparatus of Chlamydomonas reinhardtii","volume":"128","author":"Gao","year":"2018","journal-title":"Plant Physiol. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.plaphy.2004.12.007","article-title":"Cellular evidence of allelopathic interference of benzoic acid to mustard (Brassica juncea L.) seedling growth","volume":"43","author":"Kaur","year":"2005","journal-title":"Plant Physiol. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"223","DOI":"10.26651\/allelo.j.\/2018-43-2-1143","article-title":"Allelopathic potential of Tridax procumbens L. on radish and identification of allelochemicals","volume":"43","author":"Andriana","year":"2018","journal-title":"Allelopath. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1088\/1755-1315\/221\/1\/012137","article-title":"Effect of Herbicides Paraquat and Glyphosate on the Early Development of Two Tested Plants","volume":"221","author":"Tzvetkova","year":"2019","journal-title":"IOP Conf. Ser. Earth Environ. Sci."},{"key":"ref_26","unstructured":"National Pesticide Information Center (2019, July 09). Glyphosate, Technical Fact Sheet. Available online: http:\/\/npic.orst.edu\/factsheets\/archive\/glyphotech.html."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1046\/j.1445-6664.2001.00034.x","article-title":"Weed control with alfalfa pellets in transplanting rice","volume":"1","author":"Xuan","year":"2001","journal-title":"Weed Boil. Manag."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fpls.2015.01020","article-title":"Research Progress on the use of Plant Allelopathy in Agriculture and the Physiological and Ecological Mechanisms of Allelopathy","volume":"6","author":"Cheng","year":"2015","journal-title":"Front. Plant Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Van, T.M., Xuan, T.D., Minh, T.N., and Van Quan, N. (2018). Isolation and Purification of Potent Growth Inhibitors from Piper methysticum Root. Molecules, 23.","DOI":"10.3390\/molecules23081907"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.indcrop.2009.12.006","article-title":"Herbicidal activity of a medicinal plant, Peganum harmala L., and decomposition dynamics of its phytotoxins in the soil","volume":"31","author":"Sodaeizadeh","year":"2010","journal-title":"Ind. Crop. Prod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jchromb.2016.08.025","article-title":"Preparative isolation of cordycepin, N6-(2-hydroxyethyl)-adenosine and adenosine from Cordyceps militaris by macroporous resin and purification by recycling high-speed counter-current chromatography","volume":"1033","author":"Zhang","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.seppur.2016.01.043","article-title":"Effect of solvent, time and temperature on the extraction of phenolic compounds and antioxidant capacity of peach (Prunus persica L.) fruit","volume":"162","author":"Mokrani","year":"2016","journal-title":"Sep. Purif. Technol."},{"key":"ref_33","first-page":"249","article-title":"Alleviation of salt stress-induced adverse effects on maize plants by exogenous application of indoleacetic acid (IAA) and inorganic nutrients\u2014A field trial","volume":"7","author":"Kaya","year":"2013","journal-title":"Aust. J. Crop Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.scienta.2017.03.052","article-title":"UV-B radiation escalate allelopathic effect of benzoic acid on Solanum lycopersicum L.","volume":"220","author":"Bano","year":"2017","journal-title":"Sci. Hortic."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1080\/03650340601037119","article-title":"Assessment of allelopathic interference of Chenopodium album through its leachates, debris extracts, rhizosphere and amended soil","volume":"52","author":"Batish","year":"2006","journal-title":"Arch. Agron. Soil Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.scienta.2017.06.069","article-title":"Physiological and biochemical responses of two lentil varieties to chickpea (Cicer arietinum L.) aqueous extracts","volume":"225","author":"Zribi","year":"2017","journal-title":"Sci. Hortic."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/BF02279335","article-title":"Senescence of rice leaves XXXI. Changes of chlorophyll, protein, and polyamine contents and ethylene production during senescence of a chlorophyll-deficient mutant","volume":"10","author":"Chen","year":"1991","journal-title":"J. Plant Growth Regul."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.sajb.2016.03.011","article-title":"Effect of salt stress on growth, chlorophyll content, lipid peroxidation and antioxidant defence systems in Phaseolus vulgaris L.","volume":"105","author":"Abderrahim","year":"2016","journal-title":"S. Afr. J. Bot."},{"key":"ref_39","first-page":"614","article-title":"Comparative impact of genetically modified and non modified maize (Zea mays L.) on succeeding crop and associated weed","volume":"32","author":"Ullah","year":"2013","journal-title":"Toxic. Ind. Health"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1134\/S1021443718050023","article-title":"Comparative Effects of Benzoic Acid and Water Stress on Wheat Seedlings","volume":"65","author":"Amist","year":"2018","journal-title":"Russ. J. Plant Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jplph.2017.07.009","article-title":"Variation in relative water content, proline accumulation and stress gene expression in two cowpea landraces under drought","volume":"218","author":"Zegaoui","year":"2017","journal-title":"J. Plant Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.24326\/asphc.2018.2.1","article-title":"Effect of root-zone glyphosate exposure on growth and anthocyanins content of radish seedlings","volume":"17","author":"Grzesiuk","year":"2018","journal-title":"Acta Sci. Pol. Hortorum Cultus"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.4236\/ajps.2014.516265","article-title":"Chlorophyll Fluorescence as an Indicator of Cellular Damage by Glyphosate Herbicide in Raphanus sativus L. Plants","volume":"5","author":"Silva","year":"2014","journal-title":"Am. J. Plant Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.pestbp.2006.01.001","article-title":"The phenylurea cytokinin 4PU-30 protects maize plants against glyphosate action","volume":"85","author":"Sergiev","year":"2006","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_45","first-page":"177","article-title":"Effects of glyphosate on photosynthesis, chlorophyll fluorescence and physicochemical properties of cogongrass (Imperata cylindrical L.)","volume":"5","author":"Huang","year":"2012","journal-title":"Plant Omics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5941\/MYCO.2017.45.1.31","article-title":"Development of High Cordycepin-Producing Cordyceps militaris Strains","volume":"45","author":"Kang","year":"2017","journal-title":"Mycobiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s11671-015-0851-1","article-title":"Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity","volume":"10","author":"Aramwit","year":"2015","journal-title":"Nanoscale Res. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s11696-017-0266-9","article-title":"An effective and convenient synthesis of cordycepin from adenosine","volume":"72","author":"Huang","year":"2017","journal-title":"Chem. Pap."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.sajb.2015.11.006","article-title":"Cadmium stress in cotton seedlings: Physiological, photosynthesis and oxidative damages alleviated by glycinebetaine","volume":"104","author":"Farooq","year":"2016","journal-title":"S. Afr. J. Bot."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Van Quan, N., Xuan, T.D., Tran, H.-D., Thuy, N.T.D., Trang, L.T., Huong, C.T., Andriana, Y., and Tuyen, P.T. (2019). Antioxidant, \u03b1-Amylase and \u03b1-Glucosidase Inhibitory Activities and Potential Constituents of Canarium tramdenum Bark. Molecules, 24.","DOI":"10.3390\/molecules24030605"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rayee, R., Tran, H.-D., Xuan, T.D., and Khanh, T.D. (2018). Imposed Water Deficit after Anthesis for the Improvement of Macronutrients, Quality, Phytochemicals, and Antioxidants in Rice Grain. Sustainability, 10.","DOI":"10.3390\/su10124843"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.indcrop.2018.04.073","article-title":"The effect of water stress on phytochemical accumulation, bioactive compounds and expression of key genes involved in flavonoid biosynthesis in Chrysanthemum morifolium L.","volume":"120","author":"Hodaei","year":"2018","journal-title":"Ind. Crop. Prod."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Minh, T.N., Xuan, T.D., Tran, H.D., Van, T.M., Andriana, Y., Khanh, T.D., Van Quan, N., and Ahmad, A. (2019). Isolation and Purification of Bioactive Compounds from the Stem Bark of Jatropha podagrica. Molecules, 24.","DOI":"10.3390\/molecules24050889"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.3892\/etm.2016.3536","article-title":"Separation of cordycepin from Cordyceps militaris fermentation supernatant using preparative HPLC and evaluation of its antibacterial activity as an NAD+-dependent DNA ligase inhibitor","volume":"12","author":"Zhou","year":"2016","journal-title":"Exp. Ther. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/16\/2901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:10:01Z","timestamp":1760188201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/16\/2901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,9]]},"references-count":54,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["molecules24162901"],"URL":"https:\/\/doi.org\/10.3390\/molecules24162901","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,9]]}}}