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Emodin (EM), a natural anthraquinone, exhibits prominent hypolipidemic effects. However, its exact mechanism is still unclear. In this study, we successfully established hyperlipidemic zebrafish model induced by 4\u2009% high\u2010cholesterol diet (HCD) for 10\u2005days and explored the anti\u2010hyperlipidemic roles and underlying mechanisms of EM. The results indicated that EM attenuated the mortality and body mass index (BMI) of zebrafish with HLP, and ameliorated abnormal lipid levels involved in TC, TG, LDL\u2212C and HDL\u2212C levels. Besides, EM effectively reduced lipid accumulation in blood vessels and liver, alleviated hepatic histological damage, and inhibited vascular neutrophil inflammation. Finally, the mRNA expression of molecules related to lipid metabolism were studied by using real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR) to investigated the underlying mechanism. Further results found that treatment with EM up\u2010regulated AMPK\u03b1, LDLR, ABCA1 and ABCG1, and down\u2010regulated SREBP\u20102, PCSK9 and HMGCR expression. In conclusion, EM showed a prominent mitigative effect on lipid metabolism disorder in zebrafish larvae with HCD\u2010stimulated HLP, which was associated with the enhancement of LDL\u2212C uptake and reverse cholesterol transport, and inhibition of cholesterol synthesis.<\/jats:p>","DOI":"10.1002\/cbdv.202100675","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T21:59:51Z","timestamp":1638741591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Effect of Emodin on Hyperlipidemia and Hepatic Lipid Metabolism in Zebrafish Larvae Fed a High\u2010Cholesterol Diet**"],"prefix":"10.1002","volume":"19","author":[{"given":"Lin\u2010Feng","family":"He","sequence":"first","affiliation":[{"name":"National Key Laboratory of Southwestern Chinese Medicine Resources &amp; Key Laboratory of Standardization for Chinese Herbal Medicine Ministry of Education &amp; School of Pharmacy Chengdu University of Traditional Chinese Medicine  No. 1166 Liutai Avenue, Wenjiang District Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Southwestern Chinese Medicine Resources &amp; Key Laboratory of Standardization for Chinese Herbal Medicine Ministry of Education &amp; School of Pharmacy Chengdu University of Traditional Chinese Medicine  No. 1166 Liutai Avenue, Wenjiang District Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Southwestern Chinese Medicine Resources &amp; Key Laboratory of Standardization for Chinese Herbal Medicine Ministry of Education &amp; School of Pharmacy Chengdu University of Traditional Chinese Medicine  No. 1166 Liutai Avenue, Wenjiang District Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao\u2010Cheng","family":"Guo","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Southwestern Chinese Medicine Resources &amp; Key Laboratory of Standardization for Chinese Herbal Medicine Ministry of Education &amp; School of Pharmacy Chengdu University of Traditional Chinese Medicine  No. 1166 Liutai Avenue, Wenjiang District Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Southwestern Chinese Medicine Resources &amp; Key Laboratory of Standardization for Chinese Herbal Medicine Ministry of Education &amp; School of Pharmacy Chengdu University of Traditional Chinese Medicine  No. 1166 Liutai Avenue, Wenjiang District Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7211-1170","authenticated-orcid":false,"given":"Yun\u2010Xia","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Southwestern Chinese Medicine Resources &amp; Key Laboratory of Standardization for Chinese Herbal Medicine Ministry of Education &amp; School of Pharmacy Chengdu University of Traditional Chinese Medicine  No. 1166 Liutai Avenue, Wenjiang District Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"S139","article-title":"\u2018Epidemiology and management of hyperlipidemia\u2019","volume":"23","author":"Karr S.","year":"2017","journal-title":"Am. 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