{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T05:10:08Z","timestamp":1751173808656,"version":"3.41.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,4]],"date-time":"2018-02-04T00:00:00Z","timestamp":1517702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Angiogenesis is a process through which new capillaries are formed from pre\u2010existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The \u03b2\u2010D\u2010mannuronic acid (M2000) is a novel non\u2010steroidal anti\u2010inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti\u2010angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti\u2010proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen\u2010cytodex model and the chick\u00a0chorioallantoic membrane\u00a0(CAM) assay were then used to evaluate the anti\u2010angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100\u00a0\u03bcg\/mL) had no cytotoxic effect on human umbilical vein endothelial cells\u00a0(HUVECs). It was also illustrated that M2000 had little or no anti\u2010proliferative effect on HUVECs. In addition, the anti\u2010angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose\u2010dependent in the in vivo status. This study showed that M2000 could be considered as an anti\u2010angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti\u2010inflammatory effects may partly be attributable to its anti\u2010angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis\u2010related disorders.<\/jats:p>","DOI":"10.1111\/1440-1681.12907","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T13:31:50Z","timestamp":1514035910000},"page":"370-376","source":"Crossref","is-referenced-by-count":12,"title":["Anti\u2010angiogenesis effect of \u03b2\u2010D\u2010mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model"],"prefix":"10.1111","volume":"45","author":[{"given":"Mohsen","family":"Rastegari\u2010Pouyani","sequence":"first","affiliation":[{"name":"Department of Immunology School of Public Health Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Immunology School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Mostafaie","sequence":"additional","affiliation":[{"name":"Medical Biology Research Center Kermanshah University of Medical Sciences Kermanshah Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamran","family":"Mansouri","sequence":"additional","affiliation":[{"name":"Medical Biology Research Center Kermanshah University of Medical Sciences Kermanshah Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Shahabeddin","family":"Mortazavi\u2010Jahromi","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Public Health Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Cellular and Molecular Biology Kish International Campus, University of Tehran Kish Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid\u2010Reza","family":"Mohammadi\u2010Motlagh","sequence":"additional","affiliation":[{"name":"Medical Biology Research Center Kermanshah University of Medical Sciences Kermanshah Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas","family":"Mirshafiey","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-8871-3_1"},{"key":"e_1_2_7_3_1","first-page":"97","article-title":"Maternal adaptation to vasculogenesis and angiogenesis at the feto\u2010maternal interface","volume":"115","author":"Yagel S","year":"2005","journal-title":"Thromb Res"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.56.4.3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-653"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv461"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0198-013"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4255\/mcpharmacol.09.05"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-007-9074-0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.11.6.9194526"},{"key":"e_1_2_7_11_1","first-page":"PI53","article-title":"M2000: a revolution in pharmacology","volume":"11","author":"Mirshafiey A","year":"2005","journal-title":"Med Sci Monit"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2007.02.002"},{"key":"e_1_2_7_13_1","first-page":"PI105","article-title":"Chemopreventive effect of M2000, a new anti\u2010inflammatory agent","volume":"10","author":"Mirshafiey A","year":"2004","journal-title":"Med Sci Monit"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.05.022"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0031-6997(24)01448-0","article-title":"Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation","volume":"52","author":"Griffioen AW","year":"2000","journal-title":"Pharmacol Rev"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3168"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-003-0479-y"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/08923973.2015.1113296"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1013"},{"key":"e_1_2_7_20_1","first-page":"443","article-title":"Anti\u2010inflammatory property of \u03b2\u2010D\u2010mannuronic acid (M2000) on expression and activity of matrix metalloproteinase\u20102 and \u20109 through CD147 molecule in phorbol myristate acetate\u2010differentiated THP\u20101 cells","volume":"16","author":"Farahani MM","year":"2017","journal-title":"Iranian J Allergy Asthma Immunol"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2011.92"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.12280"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2005.01594.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.ima03bs111"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2005.11.257"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.1996.0002"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1440-1681.12907","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.12907","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T04:37:47Z","timestamp":1751171867000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.12907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,4]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1111\/1440-1681.12907"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.12907","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"type":"print","value":"0305-1870"},{"type":"electronic","value":"1440-1681"}],"subject":[],"published":{"date-parts":[[2018,2,4]]}}}