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This study investigates the molecular mechanisms of two lignans, 6'-Hydroxyjusticidin B (6'-HJB) and Neojusticin A (Neo-A), isolated from\n                    <jats:italic>Justicia procumbens<\/jats:italic>\n                    L., through an innovative target-driven strategy integrating LC\/MS, proteomics, network pharmacology, and biophysical validation. For the first time, integrin \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    (ITGB3) was identified as their direct molecular target, with microscale thermophoresis (MST) confirming high-affinity binding, the dissociation constant (Kd)\u2009=\u20090.0642\u2009\u00b1\u20090.005\u00a0\u03bcM for 6'-HJB; 0.0097\u2009\u00b1\u20090.001\u00a0\u03bcM for Neo-A. This study not only elucidates the structural basis of their activity-C-6 hydroxylation in 6'-HJB enhances ITGB3 specificity, whereas Neo-A\u2019s fused furan ring optimizes COX-1 interaction, but also establishes a paradigm shift from phenotypic screening to target-validated natural product research. The findings position 6'-HJB and Neo-A as promising candidates for the development of safer, ITGB3-mediated antithrombotic therapies, with future efforts directed toward structural optimization and preclinical validation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13659-025-00577-w","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T23:03:07Z","timestamp":1770073387000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Integrin \u03b23: novel antiplatelet lignans 6\u2019-Hydroxyjusticidin B and Neojusticin A from Justicia procumbens unveiled via multi-omics and biophysical validation"],"prefix":"10.1007","volume":"16","author":[{"given":"Meixian","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9533-7295","authenticated-orcid":false,"given":"Songtao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiang","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"577_CR1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1002\/art.42681","volume":"76","author":"J Leisring","year":"2024","unstructured":"Leisring J, Brodsky SV, Parikh SV. 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