{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T12:15:12Z","timestamp":1794572112830,"version":"4.9.1"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Science Centre, Poland","award":["2016\/23\/D\/NZ7\/03949"],"award-info":[{"award-number":["2016\/23\/D\/NZ7\/03949"]}]},{"DOI":"10.13039\/501100001870","name":"Foundation for Polish Science","doi-asserted-by":"crossref","award":["Start 2019"],"award-info":[{"award-number":["Start 2019"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Honeybee (<jats:italic>Apis mellifera<\/jats:italic>) venom (HBV) has been a subject of extensive proteomics research; however, scarce information on its metabolite composition can be found in the literature. The aim of the study was to identify and quantify the metabolites present in HBV. To gain the highest metabolite coverage, three different mass spectrometry (MS)-based methodologies were applied. In the first step, untargeted metabolomics was used, which employed high-resolution, accurate-mass Orbitrap MS. It allowed obtaining a broad overview of HBV metabolic components. Then, two targeted metabolomics approaches, which employed triple quadrupole MS, were applied to quantify metabolites in HBV samples. The untargeted metabolomics not only confirmed the presence of amines, amino acids, carbohydrates, and organic acids in HBV, but also provided information on venom components from other metabolite classes (e.g., nucleosides, alcohols, purine and pyrimidine derivatives). The combination of three MS-based metabolomics platforms facilitated the identification of 214 metabolites in HBV samples, among which 138 were quantified. The obtaining of the wide free amino acid profiles of HBV is one of the project\u2019s achievements. Our study contributed significantly to broadening the knowledge about HBV composition and should be continued to obtain the most comprehensive metabolite profile of HBV.<\/jats:p>","DOI":"10.1038\/s41598-020-78740-1","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T11:09:12Z","timestamp":1607598552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Identification and quantification of honeybee venom constituents by multiplatform metabolomics"],"prefix":"10.1038","volume":"10","author":[{"given":"Agnieszka","family":"Klupczynska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon","family":"Plewa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Derezi\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Garrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Y.","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenon J.","family":"Kokot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Matysiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"78740_CR1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s10555-011-9339-3","volume":"31","author":"N Or\u0161oli\u0107","year":"2012","unstructured":"Or\u0161oli\u0107, N. Bee venom in cancer therapy. Cancer Metastasis Rev. 31, 173\u2013194 (2012).","journal-title":"Cancer Metastasis Rev."},{"key":"78740_CR2","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.3389\/fimmu.2019.02090","volume":"10","author":"MB Pucca","year":"2019","unstructured":"Pucca, M. B. et al. Bee updated: Current knowledge on bee venom and bee envenoming therapy. Front. Immunol. 10, 2090 (2019).","journal-title":"Front. Immunol."},{"key":"78740_CR3","doi-asserted-by":"publisher","first-page":"507","DOI":"10.3923\/ijp.2017.507.515","volume":"13","author":"M Huerta-Reyes","year":"2017","unstructured":"Huerta-Reyes, M., Anselme, C., Cherqui, A. & Decocq, G. Exploration through the venoms from hymenoptera as potential therapeutic agents in cancer therapy. Int. J. Pharmacol. 13, 507\u2013515 (2017).","journal-title":"Int. J. Pharmacol."},{"key":"78740_CR4","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s12264-016-0024-y","volume":"32","author":"J Chen","year":"2016","unstructured":"Chen, J., Guan, S. M., Sun, W. & Fu, H. Melittin, the major pain-producing substance of bee venom. Neurosci. Bull. 32, 265\u2013272 (2016).","journal-title":"Neurosci. Bull."},{"key":"78740_CR5","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/0091-6749(77)90056-2","volume":"59","author":"BR Paull","year":"1977","unstructured":"Paull, B. R., Yunginger, J. W. & Gleich, G. J. Melittin: An allergen of honeybee venom. J. Allergy Clin. Immunol. 59, 334\u2013338 (1977).","journal-title":"J. Allergy Clin. Immunol."},{"key":"78740_CR6","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.pharmthera.2007.04.004","volume":"115","author":"DJ Son","year":"2007","unstructured":"Son, D. J. et al. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol. Ther. 115, 246\u2013270 (2007).","journal-title":"Pharmacol. Ther."},{"key":"78740_CR7","doi-asserted-by":"publisher","first-page":"4","DOI":"10.4331\/wjbc.v8.i1.4","volume":"8","author":"YN Utkin","year":"2017","unstructured":"Utkin, Y. N. Modern trends in animal venom research\u2014Omics and nanomaterials. World J. Biol. Chem. 8, 4\u201312 (2017).","journal-title":"World J. Biol. Chem."},{"key":"78740_CR8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jpba.2016.01.009","volume":"121","author":"J Matysiak","year":"2016","unstructured":"Matysiak, J., Hajduk, J., Mayer, F., Hebeler, R. & Kokot, Z. J. Hyphenated LC-MALDI-ToF\/ToF and LC-ESI-QToF approach in proteomic characterization of honeybee venom. J. Pharm. Biomed. Anal. 121, 69\u201376 (2016).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"78740_CR9","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.toxicon.2014.08.069","volume":"90","author":"J Matysiak","year":"2014","unstructured":"Matysiak, J., Hajduk, J., Pietrzak, \u0141, Schmelzer, C. E. H. & Kokot, Z. J. Shotgun proteome analysis of honeybee venom using targeted enrichment strategies. Toxicon 90, 255\u2013264 (2014).","journal-title":"Toxicon"},{"key":"78740_CR10","doi-asserted-by":"publisher","first-page":"4468","DOI":"10.3390\/toxins7114468","volume":"7","author":"EL Danneels","year":"2015","unstructured":"Danneels, E. L., Van Vaerenbergh, M., Debyser, G., Devreese, B. & de Graaf, D. C. Honeybee venom proteome profile of queens and winter bees as determined by a mass spectrometric approach. Toxins (Basel) 7, 4468\u20134483 (2015).","journal-title":"Toxins (Basel)"},{"key":"78740_CR11","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1186\/1471-2164-14-766","volume":"14","author":"R Li","year":"2013","unstructured":"Li, R. et al. Proteome and phosphoproteome analysis of honeybee (Apis mellifera) venom collected from electrical stimulation and manual extraction of the venom gland. BMC Genomics 14, 766 (2013).","journal-title":"BMC Genomics"},{"key":"78740_CR12","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1139\/z74-046","volume":"52","author":"MD Owen","year":"1974","unstructured":"Owen, M. D. & Braidwood, J. L. A quantitative and temporal study of histamine and histidine in honey bee (Apis mellifera L.) venom. Can. J. Zool. 52, 387\u201392 (1974).","journal-title":"Can. J. Zool."},{"key":"78740_CR13","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/0041-0101(82)90110-6","volume":"20","author":"MD Owen","year":"1982","unstructured":"Owen, M. D. & Bridges, A. R. Catecholamines in honey bee (Apis mellifera L.) and various vespid (Hymenoptera) venoms. Toxicon 20, 1075\u20131084 (1982).","journal-title":"Toxicon"},{"key":"78740_CR14","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/0041-0101(88)90238-3","volume":"26","author":"MD Owen","year":"1988","unstructured":"Owen, M. D. & Sloley, B. D. 5-Hydroxytryptamine in the venom of the honey bee (Apis mellifera L.): Variation with season and with insect age. Toxicon 26, 577\u2013581 (1988).","journal-title":"Toxicon"},{"key":"78740_CR15","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1139\/o68-182","volume":"46","author":"DA Nelson","year":"1968","unstructured":"Nelson, D. A. & O\u2019Connor, R. The venom of the honeybee (Apis mellifera): Free amino acids and peptides. Can. J. Biochem. 46, 1221\u20131226 (1968).","journal-title":"Can. J. Biochem."},{"key":"78740_CR16","doi-asserted-by":"crossref","unstructured":"Banks, B. E. C. & Shipolini, R. A. Chemistry and Pharmacology of Honey-bee Venom. in Venoms of the Hymenoptera 330\u2013415 (1986).","DOI":"10.1016\/B978-0-12-554770-3.50011-5"},{"key":"78740_CR17","doi-asserted-by":"publisher","first-page":"306","DOI":"10.3390\/toxins10080306","volume":"10","author":"A Klupczynska","year":"2018","unstructured":"Klupczynska, A., Pawlak, M., Kokot, Z. J. & Matysiak, J. Application of metabolomic tools for studying low molecular-weight fraction of animal venoms and poisons. Toxins Basel 10, 306 (2018).","journal-title":"Toxins Basel"},{"key":"78740_CR18","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/toxins12010014","volume":"12","author":"M Pawlak","year":"2019","unstructured":"Pawlak, M., Klupczynska, A., Kokot, Z. J. & Matysiak, J. Extending metabolomic studies of Apis mellifera venom: LC\u2013MS-based targeted analysis of organic acids. Toxins Basel 12, 14 (2019).","journal-title":"Toxins Basel"},{"key":"78740_CR19","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.3390\/toxins7041126","volume":"7","author":"M Moreno","year":"2015","unstructured":"Moreno, M. & Giralt, E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: Melittin, apamin and mastoparan. Toxins 7, 1126\u20131150 (2015).","journal-title":"Toxins"},{"key":"78740_CR20","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.toxicon.2018.04.012","volume":"148","author":"S Zhang","year":"2018","unstructured":"Zhang, S. et al. Bee venom therapy: Potential mechanisms and therapeutic applications. Toxicon 148, 64\u201373 (2018).","journal-title":"Toxicon"},{"key":"78740_CR21","doi-asserted-by":"publisher","first-page":"e004602","DOI":"10.1136\/bmjopen-2013-004602","volume":"4","author":"JA Lee","year":"2014","unstructured":"Lee, J. A. et al. Bee venom acupuncture for rheumatoid arthritis: A systematic review protocol. BMJ Open 4, e004602 (2014).","journal-title":"BMJ Open"},{"key":"78740_CR22","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jpain.2007.11.012","volume":"9","author":"MS Lee","year":"2008","unstructured":"Lee, M. S., Pittler, M. H., Shin, B. C., Kong, J. C. & Ernst, E. Bee venom acupuncture for musculoskeletal pain: A review. J. Pain 9, 289\u2013297 (2008).","journal-title":"J. Pain"},{"key":"78740_CR23","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/j.parkreldis.2012.04.030","volume":"18","author":"SY Cho","year":"2012","unstructured":"Cho, S. Y. et al. Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson\u2019s disease. Park. Relat. Disord. 18, 948\u2013952 (2012).","journal-title":"Park. Relat. Disord."},{"key":"78740_CR24","doi-asserted-by":"publisher","first-page":"374","DOI":"10.3390\/toxins11070374","volume":"11","author":"H Kim","year":"2019","unstructured":"Kim, H., Park, S. Y. & Lee, G. Potential therapeutic applications of bee venom on skin disease and its mechanisms: A literature review. Toxins Basel 11, 374 (2019).","journal-title":"Toxins Basel"},{"key":"78740_CR25","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.toxicon.2008.06.007","volume":"52","author":"WC Tu","year":"2008","unstructured":"Tu, W. C., Wu, C. C., Hsieh, H. L., Chen, C. Y. & Hsu, S. L. Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells. Toxicon 52, 318\u2013329 (2008).","journal-title":"Toxicon"},{"key":"78740_CR26","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1002\/jat.2959","volume":"34","author":"G Gajski","year":"2014","unstructured":"Gajski, G. et al. Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines. J. Appl. Toxicol. 34, 1332\u20131341 (2014).","journal-title":"J. Appl. Toxicol."},{"key":"78740_CR27","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1007\/s10616-015-9879-4","volume":"68","author":"G Gajski","year":"2016","unstructured":"Gajski, G., \u010cimbora-Zovko, T., Rak, S., Osmak, M. & Garaj-Vrhovac, V. Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin. Cytotechnology 68, 1197\u20131205 (2016).","journal-title":"Cytotechnology"},{"key":"78740_CR28","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1586\/1744666X.2015.1052409","volume":"11","author":"M Kosnik","year":"2015","unstructured":"Kosnik, M. & Korosec, P. Venom immunotherapy: Clinical efficacy, safety and contraindications. Expert Rev. Clin. Immunol. 11, 877\u2013884 (2015).","journal-title":"Expert Rev. Clin. Immunol."},{"key":"78740_CR29","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.3390\/molecules24162997","volume":"24","author":"R Wehbe","year":"2019","unstructured":"Wehbe, R. et al. Bee venom: Overview of main compounds and bioactivities for therapeutic interests. Molecules 24, 2997 (2019).","journal-title":"Molecules"},{"key":"78740_CR30","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1021\/acs.jafc.7b04160","volume":"66","author":"Y Zhao","year":"2018","unstructured":"Zhao, Y. et al. Altered serum metabolite profiling and relevant pathway analysis in rats stimulated by honeybee venom: New insight into allergy to honeybee venom. J. Agric. Food Chem. 66, 871\u2013880 (2018).","journal-title":"J. Agric. Food Chem."},{"key":"78740_CR31","doi-asserted-by":"publisher","first-page":"e103533","DOI":"10.1371\/journal.pone.0103533","volume":"9","author":"J Matysiak","year":"2014","unstructured":"Matysiak, J. et al. Effects of a honeybee sting on the serum free amino acid profile in humans. PLoS ONE 9, e103533 (2014).","journal-title":"PLoS ONE"},{"key":"78740_CR32","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/cod.12642","volume":"76","author":"T Meysman","year":"2017","unstructured":"Meysman, T. & Goossens, A. Occupational allergic contact dermatitis caused by benzisothiazolinone in printing ink and soap. Contact Dermat. 76, 51\u201353 (2017).","journal-title":"Contact Dermat."},{"key":"78740_CR33","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1039\/c9tx00135b","volume":"8","author":"S Kwak","year":"2019","unstructured":"Kwak, S. et al. Benzisothiazolinone upregulates the MUC5AC expression: Via ERK1\/2, p38, and NF-\u03baB pathways in airway epithelial cells. Toxicol. Res. Camb 8, 704\u2013710 (2019).","journal-title":"Toxicol. Res. Camb"},{"key":"78740_CR34","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.envint.2016.01.009","volume":"89\u201390","author":"F S\u00e1nchez-Bayo","year":"2016","unstructured":"S\u00e1nchez-Bayo, F. et al. Are bee diseases linked to pesticides? A brief review. Environ. Int. 89\u201390, 7\u201311 (2016).","journal-title":"Environ. Int."},{"key":"78740_CR35","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/neu.20254","volume":"66","author":"EL Moore","year":"2006","unstructured":"Moore, E. L., Haspel, G., Libersat, F. & Adams, M. E. Parasitoid wasp sting: A cocktail of GABA, taurine, and \u03b2-alanine opens chloride channels for central synaptic block and transient paralysis of a cockroach host. J. Neurobiol. 66, 811\u2013820 (2006).","journal-title":"J. Neurobiol."},{"key":"78740_CR36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.lungcan.2016.04.008","volume":"100","author":"A Klupczynska","year":"2016","unstructured":"Klupczynska, A. et al. Evaluation of serum amino acid profiles\u2019 utility in non-small cell lung cancer detection in Polish population. Lung Cancer 100, 71\u201376 (2016).","journal-title":"Lung Cancer"},{"key":"78740_CR37","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.lfs.2019.03.004","volume":"222","author":"S Plewa","year":"2019","unstructured":"Plewa, S. et al. Wide spectrum targeted metabolomics identifies potential ovarian cancer biomarkers. Life Sci. 222, 235\u2013244 (2019).","journal-title":"Life Sci."},{"key":"78740_CR38","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.numecd.2017.07.011","volume":"28","author":"K Paapstel","year":"2018","unstructured":"Paapstel, K. et al. Inverse relations of serum phosphatidylcholines and lysophosphatidylcholines with vascular damage and heart rate in patients with atherosclerosis. Nutr. Metab. Cardiovasc. Dis. 28, 44\u201352 (2018).","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"78740_CR39","doi-asserted-by":"publisher","first-page":"6357","DOI":"10.1210\/jc.2019-01104","volume":"104","author":"C Wildberg","year":"2019","unstructured":"Wildberg, C. et al. Plasma metabolomics to identify and stratify patients with impaired glucose tolerance. J. Clin. Endocrinol. Metab. 104, 6357\u20136370 (2019).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"78740_CR40","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.msard.2019.03.006","volume":"31","author":"SL Andersen","year":"2019","unstructured":"Andersen, S. L. et al. Metabolome-based signature of disease pathology in MS. Mult. Scler. Relat. Disord. 31, 12\u201321 (2019).","journal-title":"Mult. Scler. Relat. Disord."},{"key":"78740_CR41","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s00406-018-0971-6","volume":"270","author":"L Leppik","year":"2020","unstructured":"Leppik, L. et al. Profiling of lipidomics before and after antipsychotic treatment in first-episode psychosis. Eur. Arch. Psychiatry Clin. Neurosci. 270, 59\u201370 (2020).","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"78740_CR42","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3390\/toxins10100392","volume":"10","author":"A Villar-Briones","year":"2018","unstructured":"Villar-Briones, A. & Aird, S. D. Organic and peptidyl constituents of snake venoms: The picture is vastly more complex than we imagined. Toxins Basel. 10, 392 (2018).","journal-title":"Toxins Basel."},{"key":"78740_CR43","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3390\/toxins8100279","volume":"8","author":"SD Aird","year":"2016","unstructured":"Aird, S. D., Briones, A. V., Roy, M. C. & Mikheyev, A. S. Polyamines as snake toxins and their probable pharmacological functions in envenomation. Toxins Basel 8, 279 (2016).","journal-title":"Toxins Basel"},{"key":"78740_CR44","doi-asserted-by":"publisher","first-page":"514","DOI":"10.3896\/IBRA.1.53.5.05","volume":"53","author":"NS Surendra","year":"2014","unstructured":"Surendra, N. S., Ravikumar, H. & Reddy, M. R. S. Evaluation of catecholamines and amino acids from venom reservoir extract of Indian honey bee (Apis) species. J. Apic. Res. 53, 514\u2013519 (2014).","journal-title":"J. Apic. Res."},{"key":"78740_CR45","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1021\/jf0012300","volume":"49","author":"J Serra Bonvehi","year":"2001","unstructured":"Serra Bonvehi, J., Soliva Torrent\u00f3, M. & Centelles Lorente, E. Evaluation of polyphenolic and flavonoid compounds in honeybee-collected pollen produced in Spain. J. Agric. Food Chem. 49, 1848\u201353 (2001).","journal-title":"J. Agric. Food Chem."},{"key":"78740_CR46","first-page":"363","volume":"9","author":"A Canale","year":"2016","unstructured":"Canale, A. et al. Microwave-assisted drying for the conservation of honeybee pollen. Mater. Basel. 9, 363 (2016).","journal-title":"Mater. Basel."},{"key":"78740_CR47","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.sjbs.2017.08.011","volume":"26","author":"A Ranieri","year":"2019","unstructured":"Ranieri, A. et al. Freeze-drying duration influences the amino acid and rutin content in honeybee-collected chestnut pollen. Saudi J. Biol. Sci. 26, 252\u2013255 (2019).","journal-title":"Saudi J. Biol. Sci."},{"key":"78740_CR48","doi-asserted-by":"publisher","DOI":"10.1080\/00218839.2020.1801073","author":"DC De Graaf","year":"2020","unstructured":"De Graaf, D. C. et al. Standard methods for Apis mellifera venom research. J. Apic. Res. https:\/\/doi.org\/10.1080\/00218839.2020.1801073 (2020).","journal-title":"J. Apic. Res."},{"key":"78740_CR49","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/0041-0101(94)90303-4","volume":"32","author":"R Frew","year":"1994","unstructured":"Frew, R., Hamilton, M. G. & Lundy, P. M. Identification of noradrenaline in venom from the funnel-web spider Hololena curta. Toxicon 32, 511\u2013515 (1994).","journal-title":"Toxicon"},{"key":"78740_CR50","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1590\/S0104-79302001000100004","volume":"7","author":"BV Lipps","year":"2001","unstructured":"Lipps, B. V. & Khan, A. A. The presence of pharmacological substances myoglobin and histamine in venoms. J. Venom. Anim. Toxins 7, 45\u201355 (2001).","journal-title":"J. Venom. Anim. Toxins"},{"key":"78740_CR51","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/0041-0101(70)90171-6","volume":"8","author":"R Yarom","year":"1970","unstructured":"Yarom, R. & Braun, K. Cardiovascular effects of scorpion venom, morphological changes in the myocardium. Toxicon 8, 41\u201344 (1970).","journal-title":"Toxicon"},{"key":"78740_CR52","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s00359-004-0526-3","volume":"190","author":"A Weisel-Eichler","year":"2004","unstructured":"Weisel-Eichler, A. & Libersat, F. Venom effects on monoaminergic systems. J. Comp. Physiol. A. 190, 683\u2013690 (2004).","journal-title":"J. Comp. Physiol. A."},{"key":"78740_CR53","doi-asserted-by":"publisher","first-page":"e0132367","DOI":"10.1371\/journal.pone.0132367","volume":"10","author":"K Ashina","year":"2015","unstructured":"Ashina, K. et al. Histamine induces vascular hyperpermeability by increasing blood flow and endothelial barrier disruption in vivo. PLoS ONE 10, e0132367 (2015).","journal-title":"PLoS ONE"},{"key":"78740_CR54","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/0041-0101(76)90101-X","volume":"14","author":"BEC Banks","year":"1976","unstructured":"Banks, B. E. C., Hanson, J. M. & Sinclair, N. M. The isolation and identification of noradrenaline and dopamine from the venom of the honey bee Apis mellifica. Toxicon 14, 117\u2013125 (1976).","journal-title":"Toxicon"},{"key":"78740_CR55","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/0041-0101(72)90085-2","volume":"10","author":"H Edery","year":"1972","unstructured":"Edery, H., Ishay, J., Lass, I. & Gitter, S. Pharmacological activity of Oriental hornet (Vespa orientalis) venom. Toxicon 10, 13\u201325 (1972).","journal-title":"Toxicon"},{"key":"78740_CR56","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1007\/BF02147590","volume":"27","author":"MD Owen","year":"1971","unstructured":"Owen, M. D. Insect venoms: Identification of dopamine and noradrenaline in wasp and bee stings. Experientia 27, 544\u2013545 (1971).","journal-title":"Experientia"},{"key":"78740_CR57","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/0041-0101(63)90002-3","volume":"1","author":"JH Welsh","year":"1963","unstructured":"Welsh, J. H. & Batty, C. S. 5-Hydroxytryptamine content of some arthropod venoms and venom-containing parts. Toxicon 1, 165\u2013170 (1963).","journal-title":"Toxicon"},{"key":"78740_CR58","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0304-3959(03)00315-4","volume":"106","author":"W Wang","year":"2003","unstructured":"Wang, W., Wu, S. X., Wang, Y. Y., Liu, X. Y. & Li, Y. Q. 5-Hydroxytryptamine1A receptor is involved in the bee venom induced inflammatory pain. Pain 106, 135\u2013142 (2003).","journal-title":"Pain"},{"key":"78740_CR59","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/j.1476-5381.1957.tb00112.x","volume":"12","author":"JL Mongar","year":"1957","unstructured":"Mongar, J. L. Effect of chain length of aliphatic amines on histamine potentiation and release. Br. J. Pharmacol. Chemother. 12, 140\u2013148 (1957).","journal-title":"Br. J. Pharmacol. Chemother."},{"key":"78740_CR60","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/0041-008X(85)90160-7","volume":"81","author":"JY Hui","year":"1985","unstructured":"Hui, J. Y. & Taylor, S. L. Inhibition of in vivo histamine metabolism in rats by foodborne and pharmacologic inhibitors of diamine oxidase, histamine N-methyltransferase, and monoamine oxidase. Toxicol. Appl. Pharmacol. 81, 241\u2013249 (1985).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"78740_CR61","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/S0188-4409(00)00238-1","volume":"31","author":"NC De la Pe\u00f1a","year":"2000","unstructured":"De la Pe\u00f1a, N. C., Sosa-Melgarejo, J. A., Ramos, R. R. & M\u00e9ndez, J. D. Inhibition of platelet aggregation by putrescine, spermidine, and spermine in hypercholesterolemic rabbits. Arch. Med. Res. 31, 546\u2013550 (2000).","journal-title":"Arch. Med. Res."},{"key":"78740_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1515\/JBCPP.1996.7.1.1","volume":"7","author":"L Glantz","year":"2011","unstructured":"Glantz, L., Nates, J. L., Trembovler, V., Bass, R. & Shohami, E. Polyamines induce blood\u2013brain barrier disruption and edema formation in the rat. J. Basic Clin. Physiol. Pharmacol. 7, 1\u201310 (2011).","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"78740_CR63","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/0041-0101(89)90019-6","volume":"27","author":"T Abe","year":"1989","unstructured":"Abe, T., Hariya, Y., Kawai, N. & Miwa, A. Comparative study of amino acid composition in an extract from hornet venom sacs: High content of neuroactive amino acids in Vespa. Toxicon 27, 683\u2013688 (1989).","journal-title":"Toxicon"},{"key":"78740_CR64","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0065-2806(02)29002-5","volume":"29","author":"S Caveney","year":"2002","unstructured":"Caveney, S. & Cameron Donly, B. Neurotransmitter transporters in the insect nervous system. Adv. Insect Physiol. 29, 55\u2013149 (2002).","journal-title":"Adv. Insect Physiol."},{"key":"78740_CR65","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.cbpc.2008.07.010","volume":"149","author":"IM Fedorova","year":"2009","unstructured":"Fedorova, I. M., Magazanik, L. G. & Tikhonov, D. B. Characterization of ionotropic glutamate receptors in insect neuro-muscular junction. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 149, 275\u2013280 (2009).","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"78740_CR66","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/S0065-2806(08)60086-7","volume":"24","author":"PNR Usherwood","year":"1994","unstructured":"Usherwood, P. N. R. Insect glutamate receptors. Adv. In Insect Phys. 24, 309\u2013341 (1994).","journal-title":"Adv. In Insect Phys."},{"key":"78740_CR67","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/2191169a0","volume":"219","author":"PN Usherwood","year":"1968","unstructured":"Usherwood, P. N., Machili, P. & Leaf, G. l-Glutamate at insect excitatory nerve-muscle synapses. Nature 219, 1169\u20131172 (1968).","journal-title":"Nature"},{"key":"78740_CR68","doi-asserted-by":"publisher","first-page":"40","DOI":"10.2174\/1568026615666150703115919","volume":"16","author":"E Jamasbi","year":"2015","unstructured":"Jamasbi, E., Mularski, A. & Separovic, F. Model membrane and cell studies of antimicrobial activity of Melittin analogues. Curr. Top. Med. Chem. 16, 40\u201345 (2015).","journal-title":"Curr. Top. Med. Chem."},{"key":"78740_CR69","doi-asserted-by":"publisher","first-page":"10145","DOI":"10.1038\/s41598-020-66995-7","volume":"10","author":"SJ Ko","year":"2020","unstructured":"Ko, S. J. et al. Bee venom-derived antimicrobial peptide melectin has broad-spectrum potency, cell selectivity, and salt-resistant properties. Sci. Rep. 10, 10145 (2020).","journal-title":"Sci. Rep."},{"key":"78740_CR70","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/j.1432-1033.1976.tb10030.x","volume":"61","author":"J Gauldie","year":"1976","unstructured":"Gauldie, J., Hanson, J. M., Rumjanek, F. D., Shipolini, R. A. & Vernon, C. A. The peptide components of bee venom. Eur. J. Biochem. 61, 369\u2013376 (1976).","journal-title":"Eur. J. Biochem."},{"key":"78740_CR71","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3390\/toxins10110461","volume":"10","author":"Q Wu","year":"2018","unstructured":"Wu, Q., Pato\u010dka, J. & Ku\u010da, K. Insect antimicrobial peptides, a mini review. Toxins 10, 461 (2018).","journal-title":"Toxins"},{"key":"78740_CR72","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.3390\/molecules24152778","volume":"24","author":"O P\u00e9terfi","year":"2019","unstructured":"P\u00e9terfi, O., Boda, F., Szab\u00f3, Z., Ferencz, E. & B\u00e1ba, L. Hypotensive snake venom components\u2014A mini-review. Molecules 24, 2778 (2019).","journal-title":"Molecules"},{"key":"78740_CR73","doi-asserted-by":"publisher","first-page":"80","DOI":"10.3389\/fnagi.2019.00080","volume":"11","author":"KH Kim","year":"2019","unstructured":"Kim, K. H. et al. Dose-dependent neuroprotective effect of standardized bee venom phospholipase A2 against MPTP-induced Parkinson\u2019s disease in mice. Front. Aging Neurosci. 11, 80 (2019).","journal-title":"Front. Aging Neurosci."},{"key":"78740_CR74","doi-asserted-by":"publisher","first-page":"e61700","DOI":"10.1371\/journal.pone.0061700","volume":"8","author":"D Alvarez-Fischer","year":"2013","unstructured":"Alvarez-Fischer, D. et al. Bee venom and its component apamin as neuroprotective agents in a Parkinson disease mouse model. PLoS ONE 8, e61700 (2013).","journal-title":"PLoS ONE"},{"key":"78740_CR75","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s11062-019-09777-w","volume":"50","author":"MK Rakha","year":"2018","unstructured":"Rakha, M. K. et al. Neurotherapeutic effects of bee venom in a rotenone-induced mouse model of Parkinson\u2019s disease. Neurophysiology 50, 445\u2013455 (2018).","journal-title":"Neurophysiology"},{"key":"78740_CR76","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1186\/1471-2105-11-395","volume":"11","author":"T Pluskal","year":"2010","unstructured":"Pluskal, T., Castillo, S., Villar-Briones, A. & Oresic, M. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinform. 11, 395 (2010).","journal-title":"BMC Bioinform."},{"key":"78740_CR77","doi-asserted-by":"publisher","first-page":"D801","DOI":"10.1093\/nar\/gks1065","volume":"41","author":"DS Wishart","year":"2013","unstructured":"Wishart, D. S. et al. HMDB 3.0\u2014The human metabolome database in 2013. Nucleic Acids Res. 41, D801\u2013D807 (2013).","journal-title":"Nucleic Acids Res."},{"key":"78740_CR78","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1021\/acs.analchem.6b02930","volume":"89","author":"AP Siskos","year":"2017","unstructured":"Siskos, A. P. et al. Interlaboratory reproducibility of a targeted metabolomics platform for analysis of human serum and plasma. Anal. Chem. 89, 656\u2013665 (2017).","journal-title":"Anal. Chem."},{"key":"78740_CR79","doi-asserted-by":"publisher","first-page":"12","DOI":"10.20883\/jms.2019.335","volume":"88","author":"S Plewa","year":"2019","unstructured":"Plewa, S. et al. LC-MS\/MS based targeted metabolomics method for analysis of serum and cerebrospinal fluid. J. Med. Sci. 88, 12\u201320 (2019).","journal-title":"J. Med. Sci."},{"key":"78740_CR80","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1016\/j.jchromb.2011.07.030","volume":"879","author":"PK Held","year":"2011","unstructured":"Held, P. K., White, L. & Pasquali, M. Quantitative urine amino acid analysis using liquid chromatography tandem mass spectrometry and aTRAQ reagents. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 879, 2695\u20132703 (2011).","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78740-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78740-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78740-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:24:38Z","timestamp":1670372678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78740-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,10]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["78740"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-78740-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,10]]},"assertion":[{"value":"24 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21645"}}