{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:18:45Z","timestamp":1787635125522,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    In this study, we identified novel pro-angiogenic peptides from\n                    <jats:italic>Spirulina<\/jats:italic>\n                    and elucidated their molecular mechanisms. Among the three fractions (A, B, and C) purified from the\n                    <jats:italic>Spirulina<\/jats:italic>\n                    protein extract by RP-HPLC, fraction B displayed the most potent pro-angiogenic activity. Through LC-MS\/MS analysis, bioinformatics screening, and molecular docking, 20 candidate peptides were selected. In zebrafish models, five of these peptides, MFDCLR, MDMWGK, MNPGCR, MYDNFCK, and MPGLGR, significantly stimulated subintestinal vessel plexus (SIVP) growth and rescued intersegmental vessel (ISV) injury induced by Vatalanib (PTK787). Cellular experiments further showed that the five peptides reversed VEGFR tyrosine kinase inhibitor II (VRI)-induced impairments in proliferation, migration, and tube formation, with MDMWGK exhibiting the most pronounced pro-angiogenic effect. Moreover, the Matrigel plug assay confirmed that MDMWGK promoted extensive neovascularization\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Subsequent mechanistic investigations revealed that the pro-angiogenic effect of MDMWGK was associated with activation of the VEGFA\/PI3K-Akt signaling pathway, as evidenced by increased phosphorylation of PI3K and Akt. Collectively, this study provides an integrated screening strategy for discovering bioactive peptides from\n                    <jats:italic>Spirulina<\/jats:italic>\n                    and establishes a theoretical basis for developing pro-angiogenic agents.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1885188","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:23:29Z","timestamp":1787631809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Screening and characterization of pro-angiogenic peptides from Spirulina: computer simulation, experimental validation, and mechanistic insights"],"prefix":"10.3389","volume":"17","author":[{"given":"Fenghua","family":"Xu","sequence":"first","affiliation":[{"name":"Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, Basic Medical College, Qingdao University","place":["Qingdao, Shandong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences)","place":["Jinan, Shandong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences)","place":["Jinan, Shandong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohai","family":"Su","sequence":"additional","affiliation":[{"name":"Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong Province, China"]},{"name":"Department of Cardiology, Jinan Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong Province, China"]},{"name":"Department of Cardiology, Jinan Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong Province, China"]},{"name":"Shandong Provincial Key Medical and Health Discipline of Jinan Central Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"155221","DOI":"10.1016\/j.phymed.2023.155221","article-title":"Protective effect of Tibetan medicine qiwei tiexie pills on liver injury induced by acetaminophen overdose: an integrated strategy of network pharmacology, metabolomics and transcriptomics","volume":"123","author":"Bian","year":"2024","journal-title":"Phytomedicine"},{"key":"B2","doi-asserted-by":"publisher","first-page":"148082","DOI":"10.1016\/j.foodchem.2026.148082","article-title":"Research advances and outlook of bioactive peptides: integrating artificial intelligence, molecular simulation, and instrumental analysis techniques","volume":"506","author":"Cao","year":"2026","journal-title":"Food Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/nm0603-653","article-title":"Angiogenesis in health and disease","volume":"9","author":"Carmeliet","year":"2003","journal-title":"Nat. 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