{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:09:14Z","timestamp":1788858554717,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515012596"],"award-info":[{"award-number":["2025A1515012596"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2026A1515011070"],"award-info":[{"award-number":["2026A1515011070"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010721"],"award-info":[{"award-number":["2021A1515010721"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Retinopathy of prematurity (ROP) is a sight\u2010threatening vascular disorder driven by pathological neovascularization. Silibinin (SIL), a major flavonolignan from milk thistle, possesses antioxidant and anti\u2010inflammatory properties. Mechanistically, its therapeutic effect arises from attenuated oxidative stress, which suppresses mitogen\u2010activated protein kinase (MAPK) signaling upstream. This study employed an integrated network pharmacology and experimental strategy to elucidate SIL's antiangiogenic mechanism. Network analysis identified the MAPK pathway as a key target, and topological analysis highlighted core associated proteins (KDR, ABCB1, and MMP2). Subsequent in vitro experiments using human umbilical vein endothelial cells (HUVECs) showed that SIL (at concentrations of 10 and 20\u00a0\u00b5M) significantly inhibited hypoxia\u2010induced MAPK pathway activation (reducing phosphorylation of p38, ERK, and JNK) and downregulated KDR expression. SIL treatment dose\u2010dependently suppressed endothelial cell proliferation, migration, and tube formation under hypoxic conditions. In an oxygen\u2010induced retinopathy (OIR) mouse model, in vivo administration of SIL (at a dose of 100\u00a0mg\/kg) reduced pathological retinal neovascularization (RNV) by \u223c57.6% and the avascular area by \u223c27.2%. (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01 and\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05, respectively). These findings demonstrate that SIL inhibits pathological retinal angiogenesis primarily by modulating the MAPK pathway, providing mechanistic insight and highlighting its potential as a multi\u2010target therapeutic candidate for ROP.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202503861","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T17:24:36Z","timestamp":1786209876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology and Experimental Validation Elucidate the Anti\u2010Angiogenic Mechanism of Silibinin"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2848-8770","authenticated-orcid":false,"given":"Shuo\u2010Shuo","family":"Gu","sequence":"first","affiliation":[{"name":"Institute of Ophthalmology, School of Medicine Jinan University  Guangzhou China"},{"name":"Department of Ophthalmology the First Affiliated Hospital Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao\u2010Qun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Affiliated Hospital of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Zhao","family":"Yi","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, School of Medicine Jinan University  Guangzhou China"},{"name":"Department of Ophthalmology the First Affiliated Hospital Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, School of Medicine Jinan University  Guangzhou China"},{"name":"Department of Ophthalmology the First Affiliated Hospital Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Xiao","family":"Xia","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, School of Medicine Jinan University  Guangzhou China"},{"name":"Department of Ophthalmology the First Affiliated Hospital Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Hong","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases The Second Affiliated Hospital Guangzhou Medical University  Guangzhou China"},{"name":"Department of Histology and Embryology, School of Basic Medical Sciences Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai\u2010Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Affiliated Shunde Hospital of Jinan University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology the First Affiliated Hospital Jinan University  Guangzhou China"},{"name":"Department of Ophthalmology The Affiliated Shunde Hospital of Jinan University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4287-481X","authenticated-orcid":false,"given":"Hong\u2010Wei","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, School of Medicine Jinan University  Guangzhou China"},{"name":"Department of Ophthalmology the First Affiliated Hospital Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2023.109750"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2022.11.007"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13144034"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/EB.S94449"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.205"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2024.1799"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12886\u2010022\u201002591\u20109"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2024.06.007"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097914"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.12049"},{"key":"e_1_2_13_12_1","article-title":"A Narrative Review on Managing Retinopathy of Prematurity: Insights Into Pathogenesis, Screening, and Treatment Strategies","volume":"16","author":"Bishnoi K.","year":"2024","journal-title":"Cureus"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12473"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40123\u2010023\u201000744\u20107"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17101377"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986707779941159"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2023.153598"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201006\u20103955"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj231"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906\u2010021\u201003330\u20101"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.4887"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22537"},{"key":"e_1_2_13_23_1","article-title":"In Vitro Antimicrobial and Modulatory Activity of the Natural Products Silymarin and Silibinin","volume":"2015","author":"De Oliveira D. R.","year":"2015","journal-title":"BioMed Research International"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010023\u201002936\u20104"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010024\u201003172\u2010x"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13111091"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.4010"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044\u2010025\u201003383\u20108"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176906"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c25\u201000040"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071632"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2025.102022"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202402567"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13681"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120212"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3255-0_3"},{"key":"e_1_2_13_37_1","first-page":"1868","article-title":"Decursin Inhibits Retinal Neovascularization via Suppression of VEGFR\u20102 Activation","volume":"15","author":"Kim J. H.","year":"2009","journal-title":"Molecular Vision"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.118"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137354"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154658"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12091279"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03\u20100249"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29225341"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272\u2010025\u201001545\u20101"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2024.106100"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109378"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010024\u201001262\u20103"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.8.25"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2024.104689"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2025.189494"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010025\u201002114\u20109"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.139318"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16431"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/sscp.202400205"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1711653"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109347"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.39259"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202503861","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.202503861","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202503861","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:29:27Z","timestamp":1788856167000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202503861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":56,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cbdv.202503861"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202503861","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03861"}}