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Prod. Bioprospect."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thrombosis triggers various severe diseases, while antithrombotic drugs carry bleeding risks, making the development of novel natural anticoagulants a subject of widespread attention.\n                    <jats:italic>Poecilobdella manillensis<\/jats:italic>\n                    , a prevalent medicinal leech, exhibits remarkable anticoagulant and antithrombotic activities. However, the material basis underlying its anticoagulant effects remains insufficiently investigated. This study aims to mine anticoagulant peptides from\n                    <jats:italic>P. manillensis<\/jats:italic>\n                    by peptidomics analysis, elucidate the material basis of its anticoagulant activity, and provide candidate molecules for developing novel natural anticoagulant drugs. Proteins extracted from\n                    <jats:italic>P. manillensis<\/jats:italic>\n                    were enzymatically digested and fractionated using DEAE-52 and CN columns. The resulting peptide components were analyzed by UPLC-Q-Orbitrap HRMS, and peptide sequences were matched against proteomic databases using Proteome Discoverer. Anticoagulant peptides were predicted using the BIOPEP-UWM database and PeptideRanker server, followed by in vitro and in vivo activity validation. Results showed that the hydrolysate consisted predominantly of low-molecular-weight peptides. 1533 peptides with Mw\u2009&lt;\u20093000 Da (length\u2009&lt;\u200920 amino acids) were identified from the PM-A2 and PM-A3 fractions, accounting for 40.76% of the total. Four peptides selected through predictive screening demonstrated anticoagulant and antithrombotic activities in vitro. Among them, LE-11 significantly prolonged both APTT and TT (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Furthermore, LE-11 effectively alleviated carrageenan-induced thrombosis in mice, outperforming the heparin control at the mid-concentration (20 mg\/kg). In this study, the highly active anticoagulant peptide LE-11 was identified from\n                    <jats:italic>P. manillensis<\/jats:italic>\n                    through peptidomic analysis. These findings establish a solid foundation for developing anticoagulant drugs from this source and provide critical scientific support for its clinical application in treating thrombotic diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13659-025-00573-0","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:02:15Z","timestamp":1769990535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mining anticoagulant peptides from Poecilobdella manillensis by peptidomics analysis"],"prefix":"10.1007","volume":"16","author":[{"given":"Han-xue","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-li","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng-teng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-hua","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1808-4735","authenticated-orcid":false,"given":"Huan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-song","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-ping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"issue":"9","key":"573_CR1","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1056\/NEJMra0801082","volume":"359","author":"B Furie","year":"2008","unstructured":"Furie B, Furie BC. 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