{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:22:54Z","timestamp":1789050174363,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"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>Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is a nutritional metabolic disease. <jats:italic>Artemisia capillaris<\/jats:italic> (AC) is the above-ground dried part of <jats:italic>Artemisia capillaris Thunb.<\/jats:italic> or <jats:italic>Artemisia scoparia Waldst. et Kit.<\/jats:italic>, a natural medicinal plant with pharmacological effects of heat-clearing and biliary-promoting. In order to evaluate the therapeutic effect of Artemisia capillaris on NAFLD and obesity, experiments were conducted using aqueous extracts of Artemisia capillaris (WAC) to intervene in NAFLD models <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. <jats:italic>In vivo<\/jats:italic> experiments were performed using HFD-fed (high fat diet) C57BL\/6 mice to induce NAFLD model, and <jats:italic>in vitro<\/jats:italic> experiments were performed using oleic acid to induce HepG2 cells to construct NAFLD cell model. H.E. staining and oil red O staining of liver tissue were used to observe hepatocytes. Blood biochemistry analyzer was used to detect serum lipid levels in mice. The drug targets and mechanism of action of AC to improve NAFLD were investigated by western blotting, qRT-PCR and immunofluorescence. The results showed that C57BL\/6 mice fed HFD continuously for 16\u00a0weeks met the criteria for NAFLD in terms of lipid index and hepatocyte fat accumulation. WAC was able to reverse the elevation of serum lipid levels induced by high-fat diet in mice. WAC promoted the phosphorylation levels of PI3K\/AKT and AMPK in liver and HepG2 cells of NAFLD mice, inhibited SREBP-1c expression, reduced TG and lipogenesis, and decreased lipid accumulation. In summary, WAC extract activates PI3K\/AKT pathway, reduces SREBP-1c protein expression by promoting AMPK phosphorylation, and decreases fatty acid synthesis and TG content in hepatocytes. AC can be used as a potential health herb to improve NAFLD and obesity.<\/jats:p>","DOI":"10.3389\/fphar.2022.1084435","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:29:07Z","timestamp":1669620547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet"],"prefix":"10.3389","volume":"13","author":[{"given":"Meng","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Xv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixue","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"E1053","DOI":"10.1152\/ajpendo.00177.2018","article-title":"An ethanolic extract of Artemisia scoparia inhibits lipolysis in vivo and has antilipolytic effects on murine adipocytes in vitro","volume":"315","author":"Boudreau","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B2","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1039\/c8fo01236a","article-title":"Coenzyme Q10 attenuates high-fat diet-induced non-alcoholic fatty liver disease through activation of the AMPK pathway","volume":"10","author":"Chen","year":"2019","journal-title":"Food Funct."},{"key":"B4","doi-asserted-by":"publisher","first-page":"120428","DOI":"10.1016\/j.lfs.2022.120428","article-title":"Hesperidin attenuates hepatic lipid accumulation in mice fed high-fat diet and oleic acid induced HepG2 via AMPK activation","volume":"296","author":"Chen","year":"2022","journal-title":"Life Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.fct.2010.01.003","article-title":"Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice","volume":"48","author":"Cho","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.jep.2013.03.065","article-title":"Aqueous extract of Artemisia capillaris exerts hepatoprotective action in alcohol-pyrazole-fed rat model","volume":"147","author":"Choi","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1126\/science.1204265","article-title":"Human fatty liver disease: old questions and new insights","volume":"332","author":"Cohen","year":"2011","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/378785a0","article-title":"Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B","volume":"378","author":"Cross","year":"1995","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5546446","DOI":"10.1155\/2021\/5546446","article-title":"Quality evaluation of Artemisia capillaris Thunb. Based on qualitative analysis of the HPLC fingerprint and UFLC-Q-TOF-MS\/MS combined with quantitative analysis of multicomponents","volume":"2021","author":"Dai","year":"2021","journal-title":"J. Anal. Methods Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.tem.2017.05.004","article-title":"AMPK as a therapeutic target for treating metabolic diseases","volume":"28","author":"Day","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"B11","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1007\/s11892-018-1049-6","article-title":"Emerging role of AMPK in Brown and beige adipose tissue (BAT): Implications for obesity, insulin resistance, and type 2 diabetes","volume":"18","author":"Desjardins","year":"2018","journal-title":"Curr. Diab. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1056\/NEJMra1503519","article-title":"Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis","volume":"377","author":"Diehl","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1097\/meg.0000000000000736","article-title":"Transient remission of nonalcoholic fatty liver disease decreases the risk of incident type 2 diabetes mellitus in Japanese men","volume":"28","author":"Fukuda","year":"2016","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the nomenclature committee on cell death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"B15","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol. Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.celrep.2018.12.036","article-title":"Genetic liver-specific AMPK activation protects against diet-induced obesity and NAFLD","volume":"26","author":"Garcia","year":"2019","journal-title":"Cell Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ceb.2014.09.004","article-title":"AMPK: Positive and negative regulation, and its role in whole-body energy homeostasis","volume":"33","author":"Hardie","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1172\/jci15593","article-title":"SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Invest."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.3390\/biomedicines9101412","article-title":"The pharmacological effects and pharmacokinetics of active compounds of Artemisia capillaris","volume":"9","author":"Hsueh","year":"2021","journal-title":"Biomedicines"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.7150\/ijbs.27173","article-title":"The PI3K\/AKT pathway in obesity and type 2 diabetes","volume":"14","author":"Huang","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e14065","DOI":"10.1111\/jfbc.14065","article-title":"Artemisia capillaris Thunb. water extract attenuates adriamycin-induced renal injury by regulating apoptosis through the ROS\/MAPK axis","volume":"46","author":"Huang","year":"2022","journal-title":"J. Food Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"10455","DOI":"10.1074\/jbc.M117.786525","article-title":"Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice","volume":"292","author":"Irimia","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"908128","DOI":"10.3389\/fphar.2022.908128","article-title":"Protective effects and mechanisms of yinchen linggui zhugan decoction in HFD-induced nonalcoholic fatty liver disease rats based on network Pharmacology and experimental verification","volume":"13","author":"Jiang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2228","DOI":"10.1002\/mnfr.201600197","article-title":"\u03b2-Caryophyllene attenuates palmitate-induced lipid accumulation through AMPK signaling by activating CB2 receptor in human HepG2 hepatocytes","volume":"60","author":"Kamikubo","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.nut.2018.03.010","article-title":"Caffeic acid ameliorates hepatic steatosis and reduces ER stress in high fat diet-induced obese mice by regulating autophagy","author":"Kim","year":"2018","journal-title":"Nutrition"},{"key":"B27","doi-asserted-by":"publisher","first-page":"101315","DOI":"10.1016\/j.redox.2019.101315","article-title":"Peroxiredoxin 5 ameliorates obesity-induced non-alcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling","volume":"28","author":"Kim","year":"2020","journal-title":"Redox Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"867","DOI":"10.3390\/nu14040867","article-title":"Potential roles and key mechanisms of hawthorn extract against various liver diseases","volume":"14","author":"Kim","year":"2022","journal-title":"Nutrients"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1007\/s00125-006-0335-z","article-title":"Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes","volume":"49","author":"Lagathu","year":"2006","journal-title":"Diabetologia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"11224","DOI":"10.1021\/acs.jafc.2c02334","article-title":"Effect of hesperidin supplementation on liver metabolomics and gut microbiota in a high-fat diet-induced NAFLD mice model","volume":"70","author":"Li","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"132087","DOI":"10.1016\/j.foodchem.2022.132087","article-title":"Amelioration action of gastrodigenin rhamno-pyranoside from Moringa seeds on non-alcoholic fatty liver disease","volume":"379","author":"Liao","year":"2022","journal-title":"Food Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.plipres.2012.06.001","article-title":"Acyl-CoA:diacylglycerol acyltransferase: molecular biology, biochemistry and biotechnology","volume":"51","author":"Liu","year":"2012","journal-title":"Prog. Lipid Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2215274","DOI":"10.1155\/2021\/2215274","article-title":"Chlorogenic acids inhibit adipogenesis: Implications of wnt\/\u03b2-catenin signaling pathway","volume":"2021","author":"Liu","year":"2021","journal-title":"Int. J. Endocrinol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1002\/hep.28584","article-title":"Global epidemiology of nonalcoholic fatty liver disease: Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Lonardo","year":"2016","journal-title":"Hepatology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"5050","DOI":"10.1021\/acs.analchem.5b00615","article-title":"Multiple reaction monitoring-ion pair finder: a systematic approach to transform nontargeted mode to pseudotargeted mode for metabolomics study based on liquid chromatography-mass spectrometry","volume":"87","author":"Luo","year":"2015","journal-title":"Anal. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e160326","DOI":"10.1172\/jci160326","article-title":"Lipid balance must be just right to prevent development of severe liver damage","volume":"132","author":"Osborne","year":"2022","journal-title":"J. Clin. Invest."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1042\/bj20150750","article-title":"Dissecting signalling by individual Akt\/PKB isoforms, three steps at once","volume":"470","author":"Osorio-Fuentealba","year":"2015","journal-title":"Biochem. J."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.jhep.2022.04.002","article-title":"Breakthroughs in therapies for NASH and remaining challenges","volume":"76","author":"Ratziu","year":"2022","journal-title":"J. Hepatol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"353","DOI":"10.2337\/db14-0582","article-title":"Regulation of AMPK activation by CD36 links fatty acid uptake to \u03b2-oxidation","volume":"64","author":"Samovski","year":"2015","journal-title":"Diabetes"},{"key":"B40","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.jcmgh.2018.10.016","article-title":"Resolving the paradox of hepatic insulin resistance","volume":"7","author":"Santoleri","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/nrendo.2017.91","article-title":"SREBP-Regulated lipid metabolism: convergent physiology - divergent pathophysiology","volume":"13","author":"Shimano","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ebiom.2016.02.041","article-title":"Irisin inhibits hepatic cholesterol synthesis via AMPK-SREBP2 signaling","volume":"6","author":"Tang","year":"2016","journal-title":"EBioMedicine"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.3390\/cells10071822","article-title":"A narrative review on the role of AMPK on de novo lipogenesis in non-alcoholic fatty liver disease: Evidence from human studies","volume":"10","author":"von Loeffelholz","year":"2021","journal-title":"Cells"},{"key":"B44","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nrm4074","article-title":"Transcriptional regulation of hepatic lipogenesis","volume":"16","author":"Wang","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/nprot.2012.135","article-title":"Global metabolic profiling of animal and human tissues via UPLC-MS","volume":"8","author":"Want","year":"2013","journal-title":"Nat. Protoc."},{"key":"B46","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.lfs.2016.06.001","article-title":"Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipogenesis and oxidative stress","volume":"157","author":"Xie","year":"2016","journal-title":"Life Sci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4556","DOI":"10.19540\/j.cnki.cjcmm.20170928.010","article-title":"Research progress on chemical constituents, pharmacological mechanism and clinical application of Guizhi decoction","volume":"42","author":"Yuan","year":"2017","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B48","doi-asserted-by":"publisher","first-page":"854674","DOI":"10.3389\/fphar.2022.854674","article-title":"Pharmacological effects and molecular protective mechanisms of Astragalus polysaccharides on nonalcoholic fatty liver disease","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.jep.2014.08.043","article-title":"UFLC\/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from Artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis","volume":"156","author":"Zhao","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"108712","DOI":"10.1016\/j.intimp.2022.108712","article-title":"Emerging roles of sirtuins in alleviating alcoholic liver disease: A comprehensive review","volume":"108","author":"Zhao","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"826628","DOI":"10.3389\/fphar.2021.826628","article-title":"Aurantio-obtusin attenuates non-alcoholic fatty liver disease through AMPK-mediated autophagy and fatty acid oxidation pathways","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1084435\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:29:12Z","timestamp":1669620552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1084435\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":51,"alternative-id":["10.3389\/fphar.2022.1084435"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.1084435","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]},"article-number":"1084435"}}