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Here, we investigated the nature and underlying mechanisms of the effects of YiXin-Shu (YXS), an antioxidant-enriched TCM formula, on myocardial ischemia\/reperfusion (MI\/R) injury. YXS pretreatment significantly reduced infarct size and improved viable myocardium metabolism and cardiac function in hypercholesterolemic mice. Mechanistically, YXS attenuated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway (as reflected by inhibition of mitochondrial swelling, cytochrome<jats:italic>c<\/jats:italic>release and caspase-9 activity and normalization of Bcl-2 and Bax levels) without altering the death receptor and endoplasmic reticulum-stress death pathways. Moreover, YXS reduced oxidative\/nitrative stress (as reflected by decreased superoxide and nitrotyrosine content and normalized pro- and anti-oxidant enzyme levels). Interestingly, YXS upregulated endogenous nuclear receptors including LXR\u03b1, PPAR\u03b1, PPAR\u03b2 and ER\u03b1 and<jats:italic>in-vivo<\/jats:italic>knockdown of cardiac-specific LXR\u03b1 significantly blunted the cardio-protective effects of YXS. Collectively, these data show that YXS is effective in mitigating MI\/R injury by suppressing mitochondrial mediated apoptosis and oxidative stress and by upregulating LXR\u03b1, thereby providing a rationale for future clinical trials and clinical applications.<\/jats:p>","DOI":"10.1038\/srep23025","type":"journal-article","created":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T11:23:54Z","timestamp":1457695434000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["YiXin-Shu, a ShengMai-San-based traditional Chinese medicine formula, attenuates myocardial ischemia\/reperfusion injury by suppressing mitochondrial mediated apoptosis and upregulating liver-X-receptor \u03b1"],"prefix":"10.1038","volume":"6","author":[{"given":"Yichao","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchen","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,11]]},"reference":[{"key":"BFsrep23025_CR1","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1016\/j.jacc.2014.02.576","volume":"63","author":"J Pu","year":"2014","unstructured":"Pu, J. et al. 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