{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:52:29Z","timestamp":1760241149004,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T00:00:00Z","timestamp":1576281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K06726","16K08313","18K06739"],"award-info":[{"award-number":["18K06726","16K08313","18K06739"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An acylated flavonol glycoside, helichrysoside, at a dose of 10 mg\/kg\/day per os for 14 days, improved the glucose tolerance in mice without affecting the food intake, visceral fat weight, liver weight, and other plasma parameters. In this study, using hepatoblastoma-derived HepG2 cells, helichrysoside, trans-tiliroside, and kaempferol 3-O-\u03b2-D-glucopyranoside enhanced glucose consumption from the medium, but their aglycones and p-coumaric acid did not show this activity. In addition, several acylated flavonol glycosides were synthesized to clarify the structural requirements for lipid metabolism using HepG2 cells. The results showed that helichrysoside and related analogs significantly inhibited triglyceride (TG) accumulation in these cells. The inhibition by helichrysoside was more potent than that by other acylated flavonol glycosides, related flavonol glycosides, and organic acids. As for the TG metabolism-promoting activity in high glucose-pretreated HepG2 cells, helichrysoside, related analogs, and their aglycones were found to significantly reduce the TG contents in HepG2 cells. However, the desacyl flavonol glycosides and organic acids derived from the acyl groups did not exhibit an inhibitory impact on the TG contents in HepG2 cells. These results suggest that the existence of the acyl moiety at the 6'' position in the D-glucopyranosyl part is essential for glucose and lipid metabolism-promoting activities.<\/jats:p>","DOI":"10.3390\/ijms20246322","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T05:19:38Z","timestamp":1576473578000},"page":"6322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Glucose Tolerance-Improving Activity of Helichrysoside in Mice and Its Structural Requirements for Promoting Glucose and Lipid Metabolism"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-5365","authenticated-orcid":false,"given":"Toshio","family":"Morikawa","sequence":"first","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"},{"name":"Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akifumi","family":"Nagatomo","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Oka","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Miki","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihisa","family":"Taira","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Shibano-Kitahara","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro","family":"Hori","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Muraoka","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"},{"name":"Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyofumi","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"},{"name":"Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,14]]},"reference":[{"key":"ref_1","first-page":"35","article-title":"Flavonoids and their properties to form chelate complexes","volume":"76","author":"Symonowicz","year":"2012","journal-title":"Biotechnol. Food Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Santos-Buelga, C., and Feliciano, A.S. (2017). Flavonoids: From structure to health issues. Molecules, 22.","DOI":"10.3390\/molecules22030477"},{"key":"ref_3","first-page":"59","article-title":"Flavonoids: The bioactive phytochemical agent\u2014A review","volume":"2","author":"Usman","year":"2017","journal-title":"Chem. Res. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ejmech.2017.07.034","article-title":"Recent discoveries of anticancer flavonoids","volume":"142","author":"Raffa","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1134\/S0003683818030146","article-title":"Natural polyphenols: Biological activity, pharmacological potential, means of metabolic engineering (review)","volume":"54","author":"Teplova","year":"2018","journal-title":"Appl. Biochem. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1161\/CIRCRESAHA.117.309008","article-title":"Flavonoids, dairy foods, and cardiovascular and metabolic health\u2014A review of emerging biologic pathways","volume":"122","author":"Mozaffarian","year":"2018","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.abb.2018.03.022","article-title":"Research trends in flavonoids and health","volume":"646","author":"Fraga","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_8","first-page":"514","article-title":"Importance of accurate measurements in nutrition research: Dietary flavonoids as a case study","volume":"10","author":"Harnly","year":"2019","journal-title":"Food Funct."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1021\/np020058m","article-title":"New flavonol oligoglycosides and polyacylated sucroases with inhibitory effects on aldose reductase and platelet aggregation from the flowers of Prunus mume","volume":"65","author":"Yoshikawa","year":"2002","journal-title":"J. Nat. Prod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1351\/pac200274071301","article-title":"Antidiabetogenic constituents from several natural medicines","volume":"74","author":"Matsuda","year":"2002","journal-title":"Pure Appl. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1248\/cpb.56.1438","article-title":"Bioactive constituents from Chinese natural medicines. XXXII. Aminopeptidase N and aldose reductase inhibitors from Sinocrassula indica: Structures of sinocrassosides B4, B5, C1, and D1\u2013D3","volume":"56","author":"Morikawa","year":"2008","journal-title":"Chem. Pharm. Bull."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s11418-006-0105-8","article-title":"Search for bioactive constituents from several medicinal foods: Hepatoprotective, antidiabetic, and antiallergic activities","volume":"61","author":"Morikawa","year":"2007","journal-title":"J. Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1016\/S0968-0896(02)00227-4","article-title":"Structural requirements of flavonoids for inhibition of antigen-induced degranulation, TNF-\u03b1 and IL-4 production from RBL-2H3 cells","volume":"10","author":"Matsuda","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1248\/cpb.55.106","article-title":"Bioactive constituents from Chinese natural medicines. XX. Inhibitors of antigen-induced degranulation in RBL-2H3 cells from the seeds of Psoralea corylifolia","volume":"55","author":"Matsuda","year":"2007","journal-title":"Chem. Pharm. Bull."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1016\/S0968-0896(03)00067-1","article-title":"Structural requirements of flavonoids for nitric oxide production inhibitory activity and mechanism of action","volume":"11","author":"Matsuda","year":"2003","journal-title":"Bioorg. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1248\/cpb.54.1530","article-title":"Structures of new flavonoids, erycibenins D, E, and F, and NO production inhibitors from Erycibe expansa originationg in Thailand","volume":"54","author":"Morikawa","year":"2006","journal-title":"Chem. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1248\/cpb.56.956","article-title":"Medicinal foodstuffs. XXXIV. Structures of new prenylchalcones and prenylflavonones with TNF-\u03b1 and aminopeptidase N inhibitory activities from Boesenbergia rotunda","volume":"56","author":"Morikawa","year":"2008","journal-title":"Chem. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1248\/cpb.57.361","article-title":"Medicinal flowers. XXVII. New flavanone and chalcone glycosides, arenariumosides I, II, III, and IV, and tumor necrosis factor-\u03b1 inhibitors from everlasting, flowers of Helichrysum arenarium","volume":"57","author":"Morikawa","year":"2009","journal-title":"Chem. Pharm. Bull."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/cbdv.200800135","article-title":"Acylated flavonol bisdesmosides, sinocrassosides A3\u2013A7 and B3, with aminopeptidase N inhibitory activity from Sinocrassula indica","volume":"6","author":"Morikawa","year":"2009","journal-title":"Chem. Biodivers."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1248\/cpb.60.62","article-title":"Structures of two new phenolic glycosides, kaempferiaosides A and B, and hepatoprotective constituents from the rhizomes of Kaempferia parviflora","volume":"60","author":"Chaipech","year":"2012","journal-title":"Chem. Pharm. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.3987\/COM-08-11332","article-title":"Medicinal foodstuffs. XXXIII. Gastroprotective principles from Boesenbergia rotunda (Zingiberaceae)\u2014absolute stereostructures of Diels-Alder type addition prenylchalcone","volume":"75","author":"Yoshikawa","year":"2008","journal-title":"Heterocycles"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s11418-015-0955-z","article-title":"Simultaneous quantitative analysis of 12 methoxyflavones with melanogenesis inhibitory activity from the rhizomes of Kaempferia parviflora","volume":"70","author":"Ninomiya","year":"2016","journal-title":"J. Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1007\/s11418-015-0914-8","article-title":"Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium","volume":"69","author":"Morikawa","year":"2015","journal-title":"J. Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S0040-4039(00)72097-1","article-title":"The crystal and molecular structure of helichrysoside, a new acylated flavonoid glycoside from Helichrysum kraussii","volume":"14","author":"Candy","year":"1975","journal-title":"Tetrahedron Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1023\/B:CONC.0000033925.00693.7b","article-title":"Constituents of Helichrysum stoechas variety olonnense","volume":"40","author":"Lavault","year":"2004","journal-title":"Chem. Nat. Compd."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1016\/j.bmcl.2007.03.051","article-title":"Potent anti-obese principle from Rosa canina: Structural requirements and mode of action of trans-tiliroside","volume":"17","author":"Ninomiya","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.biopha.2009.08.007","article-title":"Influence of rutin treatment on biochemical alterations in experimental diabetes","volume":"64","author":"Fernandes","year":"2010","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.3945\/jn.111.137877","article-title":"Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in high-carbohydrate, high-fat diet-fed rats","volume":"141","author":"Panchal","year":"2011","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.neuroscience.2012.02.046","article-title":"Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type","volume":"210","author":"Javed","year":"2012","journal-title":"Neuroscience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jep.2013.10.036","article-title":"A review on plant-based rutin extraction methods and its pharmacological activities","volume":"150","author":"Chua","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.3390\/ijms18051074","article-title":"Synthesis and antiradical activity of isoquercitrin esters with aromatic acids and their homologues","volume":"18","author":"Chambers","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/07328303.2011.616979","article-title":"Synthesis of quercetin 3-O-[6\u2032\u2032-O-(trans-p-coumaroyl)]-\u03b2-d-glucopyranoside","volume":"30","author":"Ren","year":"2011","journal-title":"J. Carbohydr. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S1381-1177(03)00106-1","article-title":"Structural aspects of acylated plant pigments: Stabilization of flavonoid glucosides and interpretation of their functions","volume":"23","author":"Ishihara","year":"2003","journal-title":"J. Mol. Catal. B Enzym."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1021\/np000442o","article-title":"Antiprotozoal activity of the constituents of Conyza filaginoides","volume":"64","author":"Calzada","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1002\/hlca.19930760823","article-title":"Chemo-enzymatic synthesis of 6\u2032\u2032-O-(3-arylprop-2-enoyl) derivatives of the flavonol glucoside isoquercitrin","volume":"76","author":"Danieli","year":"1993","journal-title":"Helv. Chim. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/1097-0290(2000)71:3<235::AID-BIT1013>3.0.CO;2-M","article-title":"Novel enzymatic approach to the synthesis of flavonoid glycosides and their esters","volume":"71","author":"Gao","year":"2001","journal-title":"Biothech. Bioeng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.3390\/ijms15046184","article-title":"Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease","volume":"15","author":"Jung","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/XCE.0000000000000141","article-title":"Pathophysiology of cardiovascular disease in diabetes mellitus","volume":"7","author":"Nakagami","year":"2018","journal-title":"Cardiovasc Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1248\/cpb.55.1308","article-title":"Bioactive constituents from Chinese natural medicines. XXIV. Hypoglycemic effects of Sinocrassula indica in sugar-loaded rats and genetically diabetic KK-Ay mice and structures of new acylated flavonol glycosides, sinocrassosides A1, A2, B1, and B2","volume":"55","author":"Yoshikawa","year":"2007","journal-title":"Chem. Pharm. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1248\/cpb.55.308","article-title":"Medicinal flowers. XII. New spirostane-type steroid saponins with antidiabetogenic activity from Borassus flabellifer","volume":"55","author":"Yoshikawa","year":"2007","journal-title":"Chem. Pharm. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/S0968-0896(01)00422-9","article-title":"Absolute stereostructure of potent \u03b1-glucosidase inhibitor, salacinol, with unique thiosugar sulfonium sulfate inner salt structure from Salacia reticulata","volume":"10","author":"Yoshikawa","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1248\/yakushi.123.871","article-title":"Biological activities of Salacia chinensis originating in Thailand: The quality evaluation guided by \u03b1-glucosidase inhibitory activity","volume":"123","author":"Yoshikawa","year":"2003","journal-title":"Yakugaku Zasshi"},{"key":"ref_43","first-page":"145","article-title":"Antidiabetogenic constituents from Salacia species","volume":"22","author":"Matsuda","year":"2005","journal-title":"J. Tradit. Med."},{"key":"ref_44","first-page":"545","article-title":"Suippressive effect of the tablet containing Salacia chinensis extract on postprandial blood glucose","volume":"38","author":"Kobayashi","year":"2010","journal-title":"Jpn. Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.3390\/nu7031480","article-title":"Salacinol and related analogs: New leads for type 2 diabetes therapeutic candidates from the Thai traditional natural medicine Salacia chinensis","volume":"7","author":"Morikawa","year":"2015","journal-title":"Nutrients"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s11418-019-01311-w","article-title":"Salacia chinensis stem extract and its thiosugar sulfonium constituents, neokotalanol, improves HbA1c levels in ob\/ob mice","volume":"73","author":"Kabayashi","year":"2019","journal-title":"J. Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrendo.2017.80","article-title":"Regulation of hepatic glucose metabolism in health and disease","volume":"13","author":"Petersen","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101545","DOI":"10.18632\/oncotarget.21074","article-title":"Hepatoprotective potential of isoquercitrin against type 2 diabetes-induced hepatic injury in rats","volume":"8","author":"Huang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4103\/0973-1296.149708","article-title":"The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes","volume":"11","author":"Eid","year":"2015","journal-title":"Pharmacogn. Mag."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"532984","DOI":"10.1155\/2015\/532984","article-title":"Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic \u03b2-cell mass in middle-aged obese diabetic mice","volume":"2015","author":"Alkhalidy","year":"2015","journal-title":"J. Diabetes. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1002\/hep.1840200611","article-title":"Prevalence of chronic liver disease in the general population of northern Italy: The dionysos study","volume":"20","author":"Bellentani","year":"1994","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1259\/0007-1285-65-777-774","article-title":"Fatty infiltration of the liver: Analysis of prevalence, radiological and clinical features and influence on patient management","volume":"65","author":"Ibrahim","year":"1992","journal-title":"Br. J. Radiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1210\/jcem.84.5.5661","article-title":"Liver pathology and the metabolic syndrome X in severe obesity","volume":"84","author":"Marceau","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S0002-9343(99)00271-5","article-title":"Association of nonalcoholic fatty liver disease with insulin resistance","volume":"107","author":"Marchesini","year":"1999","journal-title":"Am. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7420265","DOI":"10.1155\/2018\/7420265","article-title":"Nobiletin inhibits hepatic lipogenesis via activation of AMP-activated protein kinase","volume":"2018","author":"Yuk","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.taap.2013.01.001","article-title":"Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells","volume":"267","author":"Hwang","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"569","DOI":"10.3390\/ijms17040569","article-title":"Molecular mechanisms of the anti-obesity and anti-diabetic properties of flavonoids","volume":"17","author":"Han","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.foodchem.2013.02.079","article-title":"Flavonol glycosides with lipid accumulation inhibitory activity and simultaneous quantitative analysis of 15 polyphenols and caffeine in the flower buds of Camellia sinensis from different regions by LCMS","volume":"140","author":"Morikawa","year":"2013","journal-title":"Food Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1016\/j.tet.2009.03.040","article-title":"Novel megastigmanes with lipid accumulation inhibitory and lipid metabolism-promoting activities in HepG2 cells from Sedum sarmentosum","volume":"65","author":"Muraoka","year":"2009","journal-title":"Tetrahedron"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.phytol.2013.01.004","article-title":"Acylated dolabellane-type diterpenes from Nigella sativa seeds with triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells","volume":"6","author":"Morikawa","year":"2013","journal-title":"Phytochem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1016\/j.tet.2015.03.017","article-title":"Carapanolides M\u2013S from seeds of andiroba (Carapa guianensis, Meliaceae) and triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells","volume":"71","author":"Inoue","year":"2015","journal-title":"Tetrahedron"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.freeradbiomed.2015.10.036","article-title":"SH2 domain-containing inositol 5-phosphatase (SHIP2) inhibition ameliorates high glucose-induced de-novo lipogenesis and VLDL production through regulating AMPK\/mTOR\/SREBP1 pathway and ROS production in HepG2 cells","volume":"89","author":"Meshkani","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ejphar.2017.01.009","article-title":"Flavonoid derivative (Fla-CN) inhibited adipocyte differentiation via activating AMPK and up-regulating microRNA-27 in 3T3-L1 cells","volume":"797","author":"Gan","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1016\/j.diabres.2011.02.009","article-title":"Tiliroside-derivatives enhance GLUT4 translocation via AMPK in muscle cells","volume":"92","author":"Shi","year":"2011","journal-title":"Diabetes Res. Clin. 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