{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:43:59Z","timestamp":1789541039436,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,9,26]],"date-time":"2011-09-26T00:00:00Z","timestamp":1316995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2011) <jats:bold>119<\/jats:bold>, 805\u2013814.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The principal active constituent of the botanical drug candidate PBI\u201005204, a supercritical CO<jats:sub>2<\/jats:sub> extract of <jats:italic>Nerium oleander<\/jats:italic>, is the cardiac glycoside oleandrin. PBI\u201005204 shows potent anticancer activity and is currently in phase I clinical trial as a treatment for patients with solid tumors. We have previously shown that neriifolin, which is structurally related to oleandrin, provides robust neuroprotection in brain slice and whole animal models of ischemic injury. However, neriifolin itself is not a suitable drug development candidate and the FDA\u2010approved cardiac glycoside digoxin does not cross the blood\u2013brain barrier. We report here that both oleandrin as well as the full PBI\u201005204 extract can also provide significant neuroprotection to neural tissues damaged by oxygen and glucose deprivation as occurs in ischemic stroke. Critically, we show that the neuroprotective activity of PBI\u201005204 is maintained for several hours of delay of administration after oxygen and glucose deprivation treatment. We provide evidence that the neuroprotective activity of PBI\u201005204 is mediated through oleandrin and\/or other cardiac glycoside constituents, but that additional, non\u2010cardiac glycoside components of PBI\u201005204 may also contribute to the observed neuroprotective activity. Finally, we show directly that both oleandrin and the protective activity of PBI\u201005204 are blood brain barrier penetrant in a novel model for <jats:italic>in vivo<\/jats:italic> neuroprotection. Together, these findings suggest clinical potential for PBI\u201005204 in the treatment of ischemic stroke and prevention of associated neuronal death.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2011.07439.x","type":"journal-article","created":{"date-parts":[[2011,8,20]],"date-time":"2011-08-20T10:38:55Z","timestamp":1313836735000},"page":"805-814","source":"Crossref","is-referenced-by-count":65,"title":["<i>In vitro<\/i> and <i>in vivo<\/i> neuroprotective activity of the cardiac glycoside oleandrin from <i>Nerium oleander<\/i> in brain slice\u2010based stroke models"],"prefix":"10.1111","volume":"119","author":[{"given":"Denise E.","family":"Dunn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ning","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Johansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald C.","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,9,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.181486"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1982.56.4.0482"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.02.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.04.015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015907780077105"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/0166-2236(95)80018-W","article-title":"Calcium: still center\u2010stage in hypoxic\u2010ischemic neuronal death","volume":"18","author":"Choi D. 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