{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:50:30Z","timestamp":1792047030421,"version":"4.4.0"},"reference-count":56,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2027,2]]},"DOI":"10.1016\/j.jep.2026.122498","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:13:11Z","timestamp":1791414791000},"page":"122498","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P2","title":["Bioactivity-guided identification of antithrombotic peptides from an ethanol-soluble fraction of Hirudo nipponia with anticoagulant and antiplatelet activities"],"prefix":"10.1016","volume":"374","author":[{"given":"Wanling","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunnan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouying","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2026.122498_bib1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.618411","article-title":"Advances in oral drug delivery","volume":"12","author":"Alqahtani","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2026.122498_bib2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jep.2024.118286","article-title":"Chinese medicine Di-long (Pheretima vulgaris) and its active fraction exhibit anti-rheumatoid arthritis effects by inhibiting CXCL10\/CXCR3 chemotaxis in synovium","volume":"332","author":"Bao","year":"2024","journal-title":"J. Ethnopharmacol."},{"issue":"15","key":"10.1016\/j.jep.2026.122498_bib3","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27154831","article-title":"A novel polysaccharide from AuriculariaAuricula alleviates thrombosis induced by Carrageenan in mice","volume":"27","author":"Bian","year":"2022","journal-title":"Molecules"},{"issue":"17","key":"10.1016\/j.jep.2026.122498_bib4","doi-asserted-by":"crossref","first-page":"10839","DOI":"10.1016\/S0021-9258(18)99095-2","article-title":"Stability of hirudin, a thrombin-specific inhibitor. The structure of alkaline-inactivated hirudin","volume":"266","author":"Chang","year":"1991","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jep.2026.122498_bib5","series-title":"Pharmacopoeia of the People's Republic of China","year":"2025"},{"key":"10.1016\/j.jep.2026.122498_bib6","article-title":"Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials","volume":"339","author":"De Berardis","year":"2009","journal-title":"BMJ Br. Med. J. (Clin. Res. Ed.)"},{"key":"10.1016\/j.jep.2026.122498_bib7","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/7895935","article-title":"Chinese medicinal leech: ethnopharmacology, phytochemistry, and pharmacological activities","volume":"2016","author":"Dong","year":"2016","journal-title":"Evid. Based Complement. Alternat. Med."},{"issue":"4","key":"10.1016\/j.jep.2026.122498_bib8","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s42256-025-01019-5","article-title":"InstaNovo enables diffusion-powered de novo peptide sequencing in large-scale proteomics experiments","volume":"7","author":"Eloff","year":"2025","journal-title":"Nat. Mach. Intell."},{"issue":"1","key":"10.1016\/j.jep.2026.122498_bib9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"issue":"15","key":"10.1016\/j.jep.2026.122498_bib10","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1182\/blood.2023020722","article-title":"Targeting factor XI and factor XIa to prevent thrombosis","volume":"143","author":"Gailani","year":"2024","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.jep.2026.122498_bib11","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1055\/s-0038-1648151","article-title":"Experimental studies on a recombinant hirudin, CGP 39393","volume":"65","author":"Gray","year":"1991","journal-title":"Thromb. Haemost."},{"issue":"9","key":"10.1016\/j.jep.2026.122498_bib12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0073957","article-title":"In silico approach for predicting toxicity of peptides and proteins","volume":"8","author":"Gupta","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2026.122498_bib13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-4939-2285-7_7","article-title":"Peptide toxicity prediction","volume":"1268","author":"Gupta","year":"2015","journal-title":"Methods Mol. Biol."},{"issue":"S1","key":"10.1016\/j.jep.2026.122498_bib14","first-page":"81","article-title":"Advances in bioinformatics prediction of allergenicity of novel food protein","volume":"3","author":"Hao","year":"2021","journal-title":"China Port Sci. Technol."},{"issue":"1","key":"10.1016\/j.jep.2026.122498_bib15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13045-019-0709-6","article-title":"Platelet integrin \u03b1IIb\u03b23: signal transduction, regulation, and its therapeutic targeting","volume":"12","author":"Huang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.jep.2026.122498_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.jchromb.2020.122153","article-title":"A novel thrombin inhibitory peptide discovered from leech using affinity chromatography combined with ultra-high performance liquid chromatography-high resolution mass spectroscopy","volume":"1151","author":"Huang","year":"2020","journal-title":"J. Chromatogr., B: Anal. Technol. Biomed. Life Sci."},{"issue":"3","key":"10.1016\/j.jep.2026.122498_bib17","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.3168\/jds.2019-17462","article-title":"Toxicity study and blood pressure-lowering efficacy of whey protein concentrate hydrolysate in rat models, plus peptide characterization","volume":"103","author":"Hussein","year":"2020","journal-title":"J. Dairy Sci."},{"issue":"10","key":"10.1016\/j.jep.2026.122498_bib18","first-page":"73","article-title":"Preparation of Angiotensin Converting Enzyme (ACE) inhibitory peptide from Abalone (Haliotis discus hannai) mantle membrane by serine protease in shrimp (Litopenaeus vannamei) digestive gland","volume":"43","author":"Ji","year":"2022","journal-title":"Sci. Technol. Food Industry"},{"key":"10.1016\/j.jep.2026.122498_bib19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ejps.2018.01.009","article-title":"Development and applications of a physiologically-based model of paediatric oral drug absorption","volume":"115","author":"Johnson","year":"2018","journal-title":"Eur. J. Pharmaceut. Sci."},{"issue":"3","key":"10.1016\/j.jep.2026.122498_bib20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.12938\/bmfh.32.101","article-title":"The effect of lactic acid bacteria-fermented soybean milk products on carrageenan-induced tail thrombosis in rats","volume":"32","author":"Kamiya","year":"2013","journal-title":"Biosci Microbiota Food Health"},{"key":"10.1016\/j.jep.2026.122498_bib21","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.phrs.2019.04.013","article-title":"LongShengZhi Capsule reduces carrageenan-induced thrombosis by reducing activation of platelets and endothelial cells","volume":"144","author":"Li","year":"2019","journal-title":"Pharmacol. Res."},{"issue":"Pt A","key":"10.1016\/j.jep.2026.122498_bib22","article-title":"Traditional uses, chemical constituents, pharmacological activities and toxicology of Chinese medicinal leech (Shuizhi): a comprehensive review","volume":"355","author":"Liu","year":"2026","journal-title":"J. Ethnopharmacol."},{"issue":"5","key":"10.1016\/j.jep.2026.122498_bib23","first-page":"594","article-title":"The effect of leeches extract on thrombin-induced release of TFPI and expression of TF by endothelial cells","volume":"12","author":"Liu","year":"2014","journal-title":"Chinese Journal Of integrative Medicine On Cardio-\/Cerebrovascuiar Disease"},{"issue":"1","key":"10.1016\/j.jep.2026.122498_bib24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.bbrc.2016.03.117","article-title":"A novel selective inhibitor to thrombin-induced platelet aggregation purified from the leech Whitmania pigra","volume":"473","author":"Liu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"19","key":"10.1016\/j.jep.2026.122498_bib25","first-page":"3894","article-title":"Review on scientific connotation of leech processed under high temperature","volume":"40","author":"Ma","year":"2015","journal-title":"China J. Chin. Mater. Med."},{"issue":"7181","key":"10.1016\/j.jep.2026.122498_bib26","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature06797","article-title":"Triggers, targets and treatments for thrombosis","volume":"451","author":"Mackman","year":"2008","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.jep.2026.122498_bib27","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular docking: a powerful approach for structure-based drug discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"10.1016\/j.jep.2026.122498_bib28","series-title":"The Design and Evaluation of an AntiangiogenicPeptibody","author":"Ning","year":"2019"},{"issue":"5","key":"10.1016\/j.jep.2026.122498_bib29","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1055\/s-2002-35293","article-title":"Pharmacology of recombinant hirudin","volume":"28","author":"Nowak","year":"2002","journal-title":"Semin. Thromb. Hemost."},{"issue":"5","key":"10.1016\/j.jep.2026.122498_bib30","doi-asserted-by":"crossref","DOI":"10.3390\/md18050275","article-title":"Mechanisms of bioactivities of Fucoidan from the brown seaweed fucus vesiculosus L. of the Barents Sea","volume":"18","author":"Pozharitskaya","year":"2020","journal-title":"Mar. Drugs"},{"key":"10.1016\/j.jep.2026.122498_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2019.111933","article-title":"Animal-derived medicinal products in Russia: current nomenclature and specific aspects of quality control","volume":"240","author":"Prokopov","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2026.122498_bib32","article-title":"Peptide-based targeting: novel concept for thrombosis diagnosis and treatment","volume":"95","author":"Rana","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"issue":"3","key":"10.1016\/j.jep.2026.122498_bib33","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"Reagan-Shaw","year":"2008","journal-title":"FASEB J."},{"issue":"11","key":"10.1016\/j.jep.2026.122498_bib34","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1007\/s00726-016-2299-8","article-title":"Identification and characterization of novel anticoagulant peptide with thrombolytic effect and nutrient oligopeptides with high branched chain amino acid from Whitmania pigra protein","volume":"48","author":"Ren","year":"2016","journal-title":"Amino Acids"},{"issue":"10","key":"10.1016\/j.jep.2026.122498_bib35","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1002\/jps.2600561018","article-title":"New electromechanical method for the assay of heparin in vitro","volume":"56","author":"Seip","year":"1967","journal-title":"J. Pharmaceut. Sci."},{"issue":"2","key":"10.1016\/j.jep.2026.122498_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drudis.2022.103464","article-title":"Peptide-based drug discovery: current status and recent advances","volume":"28","author":"Sharma","year":"2023","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.jep.2026.122498_bib37","article-title":"Multi-target anticoagulant regulation by peptides from medicinal leeches: a unique natural strategy against thrombosis","author":"Shi","year":"2025","journal-title":"Pharm. Res."},{"issue":"1","key":"10.1016\/j.jep.2026.122498_bib38","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s11655-025-4008-5","article-title":"Antithrombotic function of Dahuang Zhechong pill and its active ingredients: a review","volume":"32","author":"Shi","year":"2026","journal-title":"Chin. J. Integr. Med."},{"issue":"4","key":"10.1016\/j.jep.2026.122498_bib39","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.imr.2017.08.001","article-title":"Medicinal leech therapy-an overall perspective","volume":"6","author":"Sig","year":"2017","journal-title":"Integr Med Res"},{"issue":"7","key":"10.1016\/j.jep.2026.122498_bib40","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1111\/1750-3841.16215","article-title":"Tripeptide hyp-asp-gly from collagen peptides inhibited platelet activation via regulation of PI3K\/Akt-MAPK\/ERK1\/2 signaling pathway","volume":"87","author":"Song","year":"2022","journal-title":"J. Food Sci."},{"issue":"1","key":"10.1016\/j.jep.2026.122498_bib41","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.annder.2021.05.003","article-title":"Bullous haemorrhagic dermatitis induced by heparins and other anticoagulants: 94 cases from French pharmacovigilance centres and a literature review","volume":"149","author":"Uceda-Martin","year":"2022","journal-title":"Ann. Dermatol. Venereol."},{"issue":"17\u201318","key":"10.1016\/j.jep.2026.122498_bib42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/pmic.202400321","article-title":"Metaproteomics Beyond Databases: addressing the Challenges and Potentials of De Novo Sequencing","volume":"25","author":"Van den Bossche","year":"2025","journal-title":"Proteomics"},{"issue":"12","key":"10.1016\/j.jep.2026.122498_bib43","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1136\/jclinpath-2019-205922","article-title":"Distinct features of bivalent direct thrombin inhibitors, hirudin and bivalirudin, revealed by clot waveform analysis and enzyme kinetics in coagulation assays","volume":"72","author":"Wakui","year":"2019","journal-title":"J. Clin. Pathol."},{"issue":"1","key":"10.1016\/j.jep.2026.122498_bib44","doi-asserted-by":"crossref","DOI":"10.3390\/md17010047","article-title":"Novel antibacterial peptides isolated from the maillard reaction products of half-fin anchovy (Setipinna taty) hydrolysates\/glucose and their mode of action in Escherichia coli","volume":"17","author":"Wang","year":"2019","journal-title":"Mar. Drugs"},{"issue":"10","key":"10.1016\/j.jep.2026.122498_bib45","first-page":"1227","article-title":"Exploration of the functional indications,applications and dosage of leech based on a textual research on medicinal works","volume":"44","author":"Wang","year":"2024","journal-title":"Jilin J. Chin. Med."},{"key":"10.1016\/j.jep.2026.122498_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2022.154083","article-title":"Gegen Qinlian pills alleviate carrageenan-induced thrombosis in mice model by regulating the HMGB1\/NF-\u03baB\/NLRP3 signaling","volume":"100","author":"Wei","year":"2022","journal-title":"Phytomedicine"},{"issue":"20","key":"10.1016\/j.jep.2026.122498_bib47","first-page":"71","article-title":"Evolution of leech processing methods","volume":"18","author":"Wen","year":"2009","journal-title":"China Pharmaceuticals"},{"issue":"3","key":"10.1016\/j.jep.2026.122498_bib48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.4155\/fmc-2016-0188","article-title":"HemoPred: a web server for predicting the hemolytic activity of peptides","volume":"9","author":"Win","year":"2017","journal-title":"Future Med. Chem."},{"issue":"4","key":"10.1016\/j.jep.2026.122498_bib49","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/FJC.0000000000000801","article-title":"Monitoring antiplatelet aggregation In Vivo and In Vitro by microtiter plate method","volume":"75","author":"Wu","year":"2020","journal-title":"J. Cardiovasc. Pharmacol."},{"issue":"20","key":"10.1016\/j.jep.2026.122498_bib50","first-page":"230","article-title":"Didangtang: a review","volume":"29","author":"Wu","year":"2023","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"10.1016\/j.jep.2026.122498_bib51","series-title":"Isolation, Identification, and Mechanism Study of the Antithrombotic Component DPf3 from Pheretima guillelmi Based on a Multi Omics Model","author":"Wu","year":"2020"},{"key":"10.1016\/j.jep.2026.122498_bib52","series-title":"Purification and Characterizationof Antimicrobial Peptides from the Seeds of Capsella bursapastoris L. Medic and Cheiranthus cheiri L. Fujian Agriculture and Forestry University","author":"Yan","year":"2015"},{"issue":"Pt 1","key":"10.1016\/j.jep.2026.122498_bib53","article-title":"Comparative genomics of two Asian medicinal leeches Hirudo nipponia and Hirudo tianjinensis: with emphasis on antithrombotic genes and their corresponding proteins","volume":"270","author":"Zhao","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"issue":"20","key":"10.1016\/j.jep.2026.122498_bib54","first-page":"184","article-title":"Comparison of protein and polypeptide components and antithrombotic activity In Vitro of three preparations containing hirudo","volume":"31","author":"Zhong","year":"2025","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"issue":"8","key":"10.1016\/j.jep.2026.122498_bib55","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1016\/j.apsb.2021.04.001","article-title":"Oral delivery of proteins and peptides: challenges, status quo and future perspectives","volume":"11","author":"Zhu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"issue":"5","key":"10.1016\/j.jep.2026.122498_bib56","first-page":"229","article-title":"In vitro study on the antithrombotic mechanism of water decoction of leech","volume":"22","author":"Zhu","year":"2001","journal-title":"Chin. J. Biochem. Pharm."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S037887412601353X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S037887412601353X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:42:50Z","timestamp":1792046570000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S037887412601353X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2027,2]]},"references-count":56,"alternative-id":["S037887412601353X"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2026.122498","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2027,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bioactivity-guided identification of antithrombotic peptides from an ethanol-soluble fraction of Hirudo nipponia with anticoagulant and antiplatelet activities","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2026.122498","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"122498"}}