{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:06:18Z","timestamp":1770775578525,"version":"3.50.0"},"reference-count":63,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T00:00:00Z","timestamp":1524873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Squalene synthase (SQS), a key downstream enzyme involved in the cholesterol biosynthetic pathway, plays an important role in treating hyperlipidemia. Compared to statins, SQS inhibitors have shown a very significant lipid-lowering effect and do not cause myotoxicity. Thus, the paper aims to discover potential SQS inhibitors from Traditional Chinese Medicine (TCM) by the combination of molecular modeling methods and biological assays. In this study, cynarin was selected as a potential SQS inhibitor candidate compound based on its pharmacophoric properties, molecular docking studies and molecular dynamics (MD) simulations. Cynarin could form hydrophobic interactions with PHE54, LEU211, LEU183 and PRO292, which are regarded as important interactions for the SQS inhibitors. In addition, the lipid-lowering effect of cynarin was tested in sodium oleate-induced HepG2 cells by decreasing the lipidemic parameter triglyceride (TG) level by 22.50%. Finally. cynarin was reversely screened against other anti-hyperlipidemia targets which existed in HepG2 cells and cynarin was unable to map with the pharmacophore of these targets, which indicated that the lipid-lowering effects of cynarin might be due to the inhibition of SQS. This study discovered cynarin is a potential SQS inhibitor from TCM, which could be further clinically explored for the treatment of hyperlipidemia.<\/jats:p>","DOI":"10.3390\/molecules23051040","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T03:45:49Z","timestamp":1525059949000},"page":"1040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Discovery of Potential Inhibitors of Squalene Synthase from Traditional Chinese Medicine Based on Virtual Screening and In Vitro Evaluation of Lipid-Lowering Effect"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0002-6684","authenticated-orcid":false,"given":"Yankun","family":"Chen","sequence":"first","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganggang","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1859-7859","authenticated-orcid":false,"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liansheng","family":"Qiao","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"He","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Xinjiang Medical University, Urumqi 830054, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gongyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanling","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.3390\/nu5041218","article-title":"Dyslipidemia in obesity: Mechanisms and potential targets","volume":"5","author":"Klop","year":"2013","journal-title":"Nutrients"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/nature04399","article-title":"Role of cholesterol and lipid organization in disease","volume":"438","author":"Maxfield","year":"2005","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1006\/taap.1995.1058","article-title":"In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes","volume":"131","author":"Masters","year":"1995","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1021\/ml400151c","article-title":"Discovery of DF-461, a potent squalene synthase inhibitor","volume":"4","author":"Ichikawa","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/BF02693932","article-title":"Squalene synthase inhibition: A novel target for the management of dyslipidemia","volume":"9","author":"Davidson","year":"2007","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1016\/j.bmc.2012.02.054","article-title":"Discovery of novel tricyclic compounds as squalene synthase inhibitors","volume":"20","author":"Ichikawa","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18777","DOI":"10.1074\/jbc.M611763200","article-title":"Squalene synthase, a determinant of raft-associated cholesterol and modulator of cancer cell proliferation","volume":"282","author":"Brusselmans","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/jam.13053","article-title":"Genetic engineering and molecular characterization of yeast strain expressing hybrid human-yeast squalene synthase as a tool for anti-cholesterol drug assessment","volume":"120","author":"Warchol","year":"2016","journal-title":"J. Appl. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jep.2012.01.027","article-title":"Emerging approaches of traditional chinese medicine formulas for the treatment of hyperlipidemia","volume":"140","author":"Xie","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3389\/fpls.2016.01274","article-title":"Molecular cloning and functional analysis of squalene synthase 2 (SQS2) insalvia miltiorrhizabunge","volume":"7","author":"Rong","year":"2016","journal-title":"Front. Plant Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1142\/S0219633612500733","article-title":"Computational studies of squalene synthase from panax ginseng: Homology modeling, docking study and virtual screening for a new inhibitor","volume":"11","author":"Zhan","year":"2012","journal-title":"J. Theor. Comput. Chem."},{"key":"ref_12","first-page":"1315","article-title":"A combination of pharmacophore modeling, molecular docking and virtual screening for inos inhibitors from chinese herbs","volume":"24","author":"Wang","year":"2014","journal-title":"Bio. Med. Mater. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1080\/08927022.2016.1149701","article-title":"Discovery of potential novel microsomal triglyceride transfer protein inhibitors via virtual screening of pharmacophore modelling and molecular docking","volume":"42","author":"Jiang","year":"2016","journal-title":"Mol. Simul."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1161\/CIRCULATIONAHA.110.975284","article-title":"Lapaquistat acetate: Development of a squalene synthase inhibitor for the treatment of hypercholesterolemia","volume":"123","author":"Stein","year":"2011","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2923","DOI":"10.1002\/cem.2923","article-title":"Identification of hit compounds for squalene synthase: Three-dimensional quantitative structure-activity relationship pharmacophore modeling, virtual screening, molecular docking, binding free energy calculation, and molecular dynamic simulation","volume":"31","author":"Hou","year":"2017","journal-title":"J. Chemom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1016\/S0968-0896(02)00090-1","article-title":"Identification of novel mammalian squalene synthase inhibitors using a three-dimensional pharmacophore","volume":"10","author":"Fairlamb","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/aris.2009.1440430108","article-title":"Similarity methods in chemoinformatics","volume":"43","author":"Willett","year":"2009","journal-title":"Annu. Rev. Inf. Sci. Technol."},{"key":"ref_18","first-page":"1189","article-title":"Similarity in chemistry. (book reviews: Concepts and applications of molecular similarity)","volume":"252","author":"Johnson","year":"1991","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.drudis.2006.10.005","article-title":"Similarity-based virtual screening using 2d fingerprints","volume":"11","author":"Willett","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11030-013-9493-3","article-title":"An efficient multistep ligand-based virtual screening approach for GPR40 agonists","volume":"18","author":"Yao","year":"2014","journal-title":"Mol. Divers."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10822-014-9807-2","article-title":"Identification of ligand efficient, fragment-like hits from an hts library: Structure-based virtual screening and docking investigations of 2 h- and 3 h-pyrazolo tautomers for aurora kinase a selectivity","volume":"29","author":"Sarvagalla","year":"2015","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1002\/jcc.10306","article-title":"Detailed analysis of grid-based molecular docking: A case study of cdocker-a charmm-based md docking algorithm","volume":"24","author":"Wu","year":"2003","journal-title":"J. Comput. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Qiao, L., Li, B., Chen, Y., Li, L., Chen, X., Wang, L., Lu, F., Luo, G., Li, G., and Zhang, Y. (2016). Discovery of anti-hypertensive oligopeptides from adlay based on in silico proteolysis and virtual screening. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122099"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1016\/j.bmc.2014.04.005","article-title":"Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as Fak inhibitors with anticancer activity","volume":"22","author":"Duan","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30610","DOI":"10.1074\/jbc.M004132200","article-title":"Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis","volume":"275","author":"Pandit","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7015","DOI":"10.1016\/j.bmc.2015.09.034","article-title":"Antihyperlipidemic morpholine derivatives with antioxidant activity: An investigation of the aromatic substitution","volume":"23","author":"Ladopoulou","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Szefler, B., Diudea, M., Putz, M., and Grudzinski, I. (2016). Molecular dynamic studies of the complex polyethylenimine and glucose oxidase. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111796"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"757","DOI":"10.6026\/97320630010757","article-title":"Molecular modeling and molecular dynamics simulation study of the human Rab9 and RhoBTB3 C-terminus complex","volume":"10","author":"Junaid","year":"2014","journal-title":"Bioinformation"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ren, X., Zeng, R., Tortorella, M., Wang, J., and Wang, C. (2017). Structural insight into inhibition of CsrA-RNA interaction revealed by docking, molecular dynamics and free energy calculations. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-14916-6"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3654","DOI":"10.3390\/molecules19033654","article-title":"Artichoke, cynarin and cyanidin downregulate the expression of inducible nitric oxide synthase in human coronary smooth muscle cells","volume":"19","author":"Xia","year":"2014","journal-title":"Molecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1006\/taap.1997.8130","article-title":"Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes","volume":"144","author":"Gebhardt","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1021\/jf300737y","article-title":"Cynarin-rich sunflower (Helianthus annuus) sprouts possess both antiglycative and antioxidant activities","volume":"60","author":"Z","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/minf.201000082","article-title":"Targeting PKC-\u03b2 II and PKB connection: Design of dual inhibitors","volume":"30","author":"Kapil","year":"2011","journal-title":"Mol. Inf."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1248\/bpb.b13-00334","article-title":"Effect of polyphenols on 3-Hydroxy-3-methylglutaryl-Coenzyme a lyase activity in human hepatoma HepG2 cell extracts","volume":"36","author":"Nakagawa","year":"2013","journal-title":"Biol. Pharm. Bull."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/biof.5520330103","article-title":"Auraptene, a citrus fruit compound, regulates gene expression as a PPAR\u03b1 agonist in HepG2 hepatocytes","volume":"33","author":"Takahashi","year":"2008","journal-title":"Biofactors"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1016\/j.bmcl.2012.04.071","article-title":"Ethyl 2,4,6-trihydroxybenzoate is an agonistic ligand for liver X receptor that induces cholesterol efflux from macrophages without affecting lipid accumulation in HepG2 cells","volume":"22","author":"Hoang","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1093\/cvr\/cvm087","article-title":"The effect of cholesteryl ester transfer protein overexpression and inhibition on reverse cholesterol transport","volume":"77","author":"Tchoua","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s11030-016-9684-9","article-title":"Identification of potential acat-2 selective inhibitors using pharmacophore, svm and svr from chinese herbs","volume":"20","author":"Qiao","year":"2016","journal-title":"Mol. Divers."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.2174\/1871520614666140715085907","article-title":"Antineoplastic activity of monocrotaline against hepatocellular carcinoma","volume":"14","author":"Kusuma","year":"2014","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.jmgm.2007.07.002","article-title":"Pharmacophore modeling and virtual screening studies to design some potential histone deacetylase inhibitors as new leads","volume":"26","author":"Vadivelan","year":"2008","journal-title":"J. Mol. Graph. Model."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jiang, L., Li, Y., Qiao, L., Chen, X., He, Y., Zhang, Y., and Li, G. (2015). Discovery of potential negative allosteric modulators of mGluR5 from natural products using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. Can. J. Chem., 93.","DOI":"10.1139\/cjc-2015-0197"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4320201","DOI":"10.1155\/2016\/4320201","article-title":"Discovery of potential orthosteric and allosteric antagonists of P2Y1R from chinese herbs by molecular simulation methods","volume":"2016","author":"Zhang","year":"2016","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/j.bmc.2011.01.065","article-title":"Discovery of a new 2-aminobenzhydrol template for highly potent squalene synthase inhibitors","volume":"19","author":"Ichikawa","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12769","DOI":"10.3390\/molecules200712769","article-title":"Virtual screening and molecular dynamics study of potential negative allosteric modulators of mGluR1 from chinese herbs","volume":"20","author":"Jiang","year":"2015","journal-title":"Molecules"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1021\/jm010548w","article-title":"Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine Phosphatase-1B","volume":"45","author":"Doman","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.carres.2008.12.025","article-title":"GROMOS96 43a1 performance on the characterization of glycoprotein conformational ensembles through molecular dynamics simulations","volume":"344","author":"Fernandes","year":"2009","journal-title":"Carbohydr. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"Prodrg: A tool for high-throughput crystallography of protein-ligand complexes","volume":"60","author":"Schuttelkopf","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/978-94-015-7658-1_21","article-title":"Interaction models for water in relation to protein hydration","volume":"14","author":"Berendsen","year":"1981","journal-title":"Intermol. Forces"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical sampling through velocity rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1080\/07391102.2012.706403","article-title":"Modelling family 2 cystatins and their interaction with papain","volume":"31","author":"Nandy","year":"2013","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yang, S.C., Chang, S.S., Chen, H.Y., and Chen, Y.C. (2011). Identification of potent EGFR inhibitors from TCM database@taiwan. PLoS Comput. Biol., 7.","DOI":"10.1371\/journal.pcbi.1002189"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ke, Y.Y., Singh, V.K., Coumar, M.S., Hsu, Y.C., Wang, W.C., Song, J.S., Chen, C.H., Lin, W.H., Wu, S.H., and Hsu, J.T. (2015). Homology modeling of DFG-in FMS-like tyrosine kinase 3 (FLT3) and structure-based virtual screening for inhibitor identification. Sci. Rep., 5.","DOI":"10.1038\/srep11702"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Rampogu, S., Baek, A., Zeb, A., and Lee, K.W. (2018). Exploration for novel inhibitors showing back-to-front approach against vegfr-2 kinase domain (4AG8) employing molecular docking mechanism and molecular dynamics simulations. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4050-1"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Fu, Y., Sun, Y.N., Yi, K.H., Li, M.Q., Cao, H.F., Li, J.Z., and Ye, F. (2018). Combination of virtual screening protocol by in silico toward the discovery of novel 4-hydroxyphenylpyruvate dioxygenase inhibitors. Front. Chem., 6.","DOI":"10.3389\/fchem.2018.00014"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"G_mmpbsa--a gromacs tool for high-throughput mm-pbsa calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification, Can. J. Biochem. Physiol. 37, 911\u2013917","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1476-511X-11-38","article-title":"Bioactivity-guided fractionation of the triglyceride-lowering component and in vivo and in vitro evaluation of hypolipidemic effects of Calyx seu fructus physalis","volume":"11","author":"Yang","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lu, F., Luo, G., Qiao, L., Jiang, L., Li, G., and Zhang, Y. (2016). Virtual screening for potential allosteric inhibitors of cyclin-dependent kinase 2 from traditional chinese medicine. Molecules, 21.","DOI":"10.3390\/molecules21091259"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1002\/jsfa.4489","article-title":"Mulberry extract inhibits oleic acid-induced lipid accumulation via reduction of lipogenesis and promotion of hepatic lipid clearance","volume":"91","author":"Ou","year":"2011","journal-title":"J. Sci. Food Agric."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0014-2999(01)01450-9","article-title":"Squalene synthase inhibitors reduce plasma triglyceride through a low-density lipoprotein receptor-independent mechanism","volume":"431","author":"Hiyoshi","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ejphar.2006.02.006","article-title":"Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis","volume":"535","author":"Tavridou","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7402","DOI":"10.1016\/j.bmc.2010.09.008","article-title":"Design of more potent squalene synthase inhibitors with multiple activities","volume":"18","author":"Kourounakis","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Shao, Y., Qiao, L., Wu, L., Sun, X., Zhu, D., Yang, G., Zhang, X., Mao, X., Chen, W., and Liang, W. (2016). Structure identification and anti-cancer pharmacological prediction of triterpenes from Ganoderma lucidum. Molecules, 21.","DOI":"10.3390\/molecules21050678"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/5\/1040\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:02:35Z","timestamp":1760194955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/5\/1040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,28]]},"references-count":63,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["molecules23051040"],"URL":"https:\/\/doi.org\/10.3390\/molecules23051040","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,28]]}}}