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The potential risk of drug\u2013drug interactions (DDIs) arising from co-administration of <jats:italic>Aconitum<\/jats:italic> alkaloids and other drugs against specific targets such as P-glycoprotein (P-gp) must be evaluated. This study focused on the effects of three representative <jats:italic>Aconitum<\/jats:italic> alkaloids: aconitine (AC), benzoylaconine (BAC), and aconine, on the expression and activity of P-gp. We observed that <jats:italic>Aconitum<\/jats:italic> alkaloids increased P-gp expression in LS174T and Caco-2 cells in the order AC\u2009&gt;\u2009BAC\u2009&gt;\u2009aconine. Nuclear receptors were involved in the induction of P-gp. AC and BAC increased the P-gp transport activity. Strikingly, intracellular ATP levels and mitochondrial mass also increased. Furthermore, exposure to AC decreased the toxicity of vincristine and doxorubicin towards the cells. <jats:italic>In vivo<\/jats:italic>, AC significantly up-regulated the P-gp protein levels in the jejunum, ileum, and colon of FVB mice, and protected them against acute AC toxicity. Taken together, the findings of our <jats:italic>in vi<\/jats:italic>tro and <jats:italic>in vivo<\/jats:italic> experiments indicate that AC can induce P-gp expression, and that co-administration of AC with P-gp substrate drugs may cause DDIs. Our findings have important implications for <jats:italic>Aconitum<\/jats:italic> therapy in clinics.<\/jats:p>","DOI":"10.1038\/srep25343","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T09:38:10Z","timestamp":1462268290000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Induction of P-glycoprotein expression and activity by Aconitum alkaloids: Implication for clinical drug\u2013drug interactions"],"prefix":"10.1038","volume":"6","author":[{"given":"Jinjun","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shugui","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rilan","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,3]]},"reference":[{"key":"BFsrep25343_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jep.2009.07.031","volume":"126","author":"J Singhuber","year":"2009","unstructured":"Singhuber, J., Zhu, M., Prinz, S. & Kopp, B. 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