{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:56:02Z","timestamp":1789480562864,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether <jats:italic>Artemisia frigida<\/jats:italic>, a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to identify the active substances in <jats:italic>A. frigida<\/jats:italic>, a phytochemistry investigation was conducted using a bioassay-guided isolation method. Consequently, one terpene (<jats:bold>1<\/jats:bold>) and one flavone (<jats:bold>2<\/jats:bold>) were identified. Compound <jats:bold>1<\/jats:bold> ((+)-dehydrovomifoliol) exhibited potent effects against lipid accumulation in OA-induced HepG2 cells, without causing cyto-toxicity. Notably, treatment with (+)-dehydrovomifoliol decreased the expression levels of three genes related to lipogenesis (<jats:italic>SREBP1, ACC,<\/jats:italic> and <jats:italic>FASN<\/jats:italic>) and increased those of three genes related to fatty acid oxidation (<jats:italic>PPAR\u03b1, ACOX1,<\/jats:italic> and <jats:italic>FGF21<\/jats:italic>). In addition, similar results were observed for SREBP1, PPAR\u03b1, and FGF21 protein levels. The effects of (+)-dehydrovomifoliol were partially reversed by treatment with the PPAR\u03b1 antagonist GW6471, indicating the important role of the PPAR\u03b1\u2013FGF21 axis in the effects of (+)-dehydrovomifoliol. Based on its effects on hepatic lipogenesis and fatty acid oxidation signaling via the PPAR\u03b1\u2013FGF21 axis, (+)-dehydrovomifoliol isolated from <jats:italic>A. frigida<\/jats:italic> could be a useful early lead compound for developing new drugs for NAFLD prevention.<\/jats:p>","DOI":"10.3389\/fphar.2021.750147","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T07:47:19Z","timestamp":1637308039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPAR\u03b1\u2013FGF21 Pathway"],"prefix":"10.3389","volume":"12","author":[{"given":"Yiyuan","family":"Xi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jujia","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namki","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"603","DOI":"10.3945\/jn.110.135210","article-title":"PPARalpha Expression Protects Male Mice from High Fat-Induced Nonalcoholic Fatty Liver","volume":"141","author":"Abdelmegeed","year":"2011","journal-title":"J. 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