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We investigated the hepatoprotective effects of SDT against oxidative stress and attempted to clarify the underlying molecular mechanisms. SDT pretreatment reduced arachidonic acid (AA) plus iron\u2010mediated cytotoxicity in a concentration\u2010dependent manner and prevented changes in apoptosis\u2010related protein expression. In addition, SDT pretreatment significantly reduced glutathione depletion, hydrogen peroxide production, and mitochondrial dysfunction via treatment with AA plus iron. SDT increased the phosphorylation of AMP\u2010activated protein kinase (AMPK) in accordance with the phosphorylation of Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase kinase 2 (CaMKK2). Experiments using an AMPK chemical inhibitor (Compound C) or CaMKK2 chemical inhibitor (STO\u2010609) suggested that the CaMKK2\u2010AMPK signaling pathway contributes to SDT\u2010mediated protection of mitochondria and cells. Moreover, administration of SDT for 4 consecutive days to mice significantly reduced the alanine aminotransferase and aspartate aminotransferase activities induced by carbon tetrachloride, and the numbers of degenerated hepatocytes, infiltrated inflammatory cells, nitrotyrosine\u2010positive cells, and 4\u2010hydroxynonenal\u2010positive cells in liver tissue. Therefore, SDT protects hepatocytes from oxidative stress via CaMKK2\u2010dependent AMPK activation and has the therapeutic potential to prevent or treat oxidative stress\u2010related liver injury.<\/jats:p>","DOI":"10.1155\/2018\/8609285","type":"journal-article","created":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T23:50:32Z","timestamp":1541548232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>Sipjeondaebo-tang<\/i> Alleviates Oxidative Stress\u2010Mediated Liver Injury through Activation of the CaMKK2\u2010AMPK Signaling Pathway"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3845-6268","authenticated-orcid":false,"given":"Sang Mi","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0988-7763","authenticated-orcid":false,"given":"Sung 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