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The pharmacological value of CBN is well demonstrated, especially in the prevention of several cancers and analgesic activity. A striking therapeutic target for arterial thrombosis is inhibition of platelet activation because platelet activation significantly contributes to these diseases. The current study examined the influence of CBN on human platelet activation in vitro and vascular thrombotic formation in vivo.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Aggregometry, immunoblotting, immunoprecipitation, confocal microscopic analysis, fibrin clot retraction, and thrombogenic animals were used in this study.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>CBN markedly inhibited platelet aggregation in washed human platelets stimulated only by collagen, but was not effective in platelets stimulated by other agonists such as thrombin, arachidonic acid, and U46619. CBN evidently inhibited ATP release, intracellular ([Ca<jats:sup>2+<\/jats:sup>]i) mobilization, and P-selectin expression. It also inhibited the phosphorylation of phospholipase C (PLC)\u03b32, protein kinase C (PKC), Akt (protein kinase B), and mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase [ERK] 1\/2 and c-Jun N-terminal kinase [JNK] 1\/2, but not p38 MAPK) in collagen-activated platelets. Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the CBN-mediated inhibition of platelet aggregation. CBN had no significant effect in triggering vasodilator-stimulated phosphoprotein phosphorylation. Moreover, it markedly hindered integrin \u03b1<jats:sub>IIb<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> activation by interfering with the binding of PAC-1; nevertheless, it had no influences on integrin \u03b1<jats:sub>IIb<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>-mediated outside-in signaling such as adhesion number and spreading area of platelets on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Additionally, CBN did not attenuate FITC-triflavin binding or phosphorylation of proteins, such as integrin \u03b2<jats:sub>3<\/jats:sub>, Src, and focal adhesion kinase, in platelets spreading on immobilized fibrinogen. In experimental mice, CBN increased the occlusion time of thrombotic platelet plug formation.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study demonstrated that CBN exhibits an exceptional activity against platelet activation through inhibition of the PLC\u03b32-PKC cascade, subsequently suppressing the activation of Akt and ERKs\/JNKs and influencing platelet aggregation. Consequently, this work provides solid evidence and considers that CBN has the potential to serve as a therapeutic agent for the treatment of thromboembolic disorders.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12929-020-0619-5","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T04:13:46Z","timestamp":1588738426000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Modulation of human platelet activation and in vivo vascular thrombosis by columbianadin: regulation by integrin \u03b1IIb\u03b23 inside-out but not outside-in signals"],"prefix":"10.1186","volume":"27","author":[{"given":"Shaw-Min","family":"Hou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Wei","family":"Hsia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Lin","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Hsuan","family":"Hsia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanasekaran","family":"Jayakumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marappan","family":"Velusamy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-3678","authenticated-orcid":false,"given":"Joen-Rong","family":"Sheu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"issue":"8","key":"619_CR1","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/S0006-2952(00)00417-2","volume":"60","author":"B Payrastre","year":"2000","unstructured":"Payrastre B, Missy K, Trumel C, Bodin S, Plantavid M, Chap H. 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