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Here, we investigated the effects of the flavonoid silibinin on hypoxia\u2010induced angiogenesis in a rat AMD<\/jats:styled-content> model.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Retinal pigmented epithelial (RPE<\/jats:styled-content>) cells were subjected to hypoxia in vitro<\/jats:italic> and the effects of silibinin on activation of key hypoxia\u2010induced pathways were examined by elucidating the hypoxia\u2010inducible factor\u20101 alpha (HIF<\/jats:styled-content>\u20101\u03b1<\/jats:styled-content>) protein level by W<\/jats:styled-content>estern blot. A rat model of AMD<\/jats:styled-content> was developed by intravitreal injection of VEGF<\/jats:styled-content> in B<\/jats:styled-content>rown N<\/jats:styled-content>orway rats, with or without concomitant exposure of animals to hypoxia. Animals were treated with oral silibinin starting at day 7 post\u2010VEGF<\/jats:styled-content> injection and AMD<\/jats:styled-content> changes were followed by fluorescein angiography on days 14 and 28 post\u2010injection.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Silibinin pretreatment of RPE<\/jats:styled-content> cells increased proline hydroxylase\u20102 expression, inhibited HIF<\/jats:styled-content>\u20101\u03b1<\/jats:styled-content> subunit accumulation, and inhibited VEGF<\/jats:styled-content> secretion. Silibinin\u2010induced HIF<\/jats:styled-content>\u20101\u03b1<\/jats:styled-content> and VEGF<\/jats:styled-content> down\u2010regulation required suppression of hypoxia\u2010induced phosphatidylinositol 3\u2010kinase\/Akt<\/jats:styled-content>\/mammalian target of rapamycin (mTOR<\/jats:styled-content>) pathway. In the rat model of AMD<\/jats:styled-content>, silibinin administration prevented VEGF<\/jats:styled-content>\u2010 and VEGF<\/jats:styled-content> plus hypoxia\u2010induced retinal oedema and neovascularization.<\/jats:p><\/jats:sec>Conclusion and Implications<\/jats:title>The effects of silibinin, both in vitro<\/jats:italic> and in vivo,<\/jats:italic> support its potential as a therapeutic for the prevention of neovascular AMD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.02227.x","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T17:52:13Z","timestamp":1348595533000},"page":"920-931","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Silibinin inhibits VEGF<\/scp> secretion and age\u2010related macular degeneration in a hypoxia\u2010dependent manner through the PI<\/scp>\u20103 kinase\/Akt<\/scp>\/mTOR<\/scp> 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