{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:16:17Z","timestamp":1789676177036,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"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>In the search for natural products having a dual inhibitory action on diabetes and Alzheimer\u2019s disease, this study investigated the activity of different parts of Korean thistle (Cirsium japonicum var. maackii (Maxim.) Matsum), and its fractional constituents by in vitro enzymatic and in silico molecular docking studies. Cirsium maackii has been used as a traditional medicine for the treatment of several diseases. The ethyl acetate and dichloromethane fractions of a leaf extract showed \u03b1-glucosidase and BACE1 inhibitory activity, respectively. Furthermore, the isolated compound, luteolin, exhibited concentration-dependent non-competitive inhibition against both \u03b1-glucosidase and BACE1 (IC50 = 51.27 \u00b1 1.23 and 13.75 \u00b1 0.26 \u03bcM; Ki value = 52.04 and 14.76 \u03bcM, respectively). Moreover, docking studies showed that luteolin formed a strong hydrogen bond with the peripheral binding amino acid residues, and hydrophobic interactions with the \u03b1-glucosidase and BACE1 enzymes. Therefore, Korean thistle may act as an important dietary supplement against diabetes and Alzheimer\u2019s disease, especially the leaves, because of the preponderance of the active component, luteolin, making Korean thistle a promising candidate for more detailed in vitro and in vivo studies.<\/jats:p>","DOI":"10.3390\/molecules24030649","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T02:49:44Z","timestamp":1550026184000},"page":"649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.): A Potential Dietary Supplement against Diabetes and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9112-1630","authenticated-orcid":false,"given":"Aditi","family":"Wagle","sequence":"first","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Hui","family":"Seong","sequence":"additional","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3761-9424","authenticated-orcid":false,"given":"Srijan","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ah","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-8868","authenticated-orcid":false,"given":"Jae Sue","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1177\/193229680800200619","article-title":"Alzheimer\u2019s disease is type 3 diabetes\u2014Evidence reviewed","volume":"2","author":"Wands","year":"2008","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"474","DOI":"10.2337\/diabetes.53.2.474","article-title":"Increased risk of type 2 diabetes in Alzheimer disease","volume":"53","author":"Janson","year":"2004","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.carres.2003.10.035","article-title":"Two potent competitive inhibitors discriminating \u03b1-glucosidase family I from family II","volume":"339","author":"Kimura","year":"2004","journal-title":"Carbohydr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/0973-7847.79096","article-title":"\u03b1-Glucosidase inhibitors from plants: A natural approach to treat diabetes","volume":"5","author":"Kumar","year":"2011","journal-title":"Pharmacogn. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/anie.198107441","article-title":"Chemistry and biochemistry of microbial \u03b1-glucosidase inhibitors","volume":"20","author":"Truscheit","year":"1981","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"(2018). Alzheimer\u2019s Association, 2018 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 14, 367\u2013429.","DOI":"10.1016\/j.jalz.2018.02.001"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Du, X., Wang, X., and Geng, M. (2018). Alzheimer\u2019s disease hypothesis and related therapies. Transl. Neurodegener., 7.","DOI":"10.1186\/s40035-018-0107-y"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.molmed.2005.08.004","article-title":"Proteolytic mechanisms in amyloid-\u03b2 metabolism: Therapeutic implications for Alzheimer\u2019s disease","volume":"11","author":"Vardy","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.286.5440.735","article-title":"\u03b2-secretase cleavage of Alzheimer\u2019s amyloid precursor protein by the transmembrane aspartic protease BACE","volume":"286","author":"Vassar","year":"1999","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"889","DOI":"10.4239\/wjd.v5.i6.889","article-title":"Type 2 diabetes mellitus and Alzheimer\u2019s disease","volume":"5","author":"Barbagallo","year":"2014","journal-title":"World J. Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/aje\/kwn229","article-title":"Association of adiposity status and changes in early to mid-adulthood with incidence of Alzheimer\u2019s disease","volume":"168","author":"Beydoun","year":"2008","journal-title":"Am. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"549","DOI":"10.2147\/CIA.S74042","article-title":"Link between type 2 diabetes and Alzheimer\u2019s disease: From epidemiology to mechanism and treatment","volume":"10","author":"Li","year":"2015","journal-title":"Clin. Interv. Aging"},{"key":"ref_14","unstructured":"Kim, J.G. (1984). Illustrated Natural Drugs Encyclopedia, Namsandang."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.intimp.2006.02.002","article-title":"Tumor inhibition and improved immunity in mice treated with flavone from Cirsium japonicum DC","volume":"6","author":"Liu","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1016\/j.fct.2012.04.011","article-title":"Anti-inflammatory activity of Korean thistle Cirsium maackii and its major flavonoid, luteolin 5-O-glucoside","volume":"50","author":"Jung","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jep.2017.07.027","article-title":"Protective effects of flavonoids isolated from Korean milk thistle Cirsium japonicum var. maackii (Maxim.) Matsum on tert-butyl hydroperoxide-induced hepatotoxicity in HepG2 cells","volume":"209","author":"Jung","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1016\/j.bmcl.2017.07.070","article-title":"Beneficial effects of a medicinal herb, Cirsium japonicum var. maackii, extract and its major component, cirsimaritin on breast cancer metastasis in MDA-MB-231 breast cancer cells","volume":"27","author":"Park","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1995-7645(14)60178-4","article-title":"Inhibition of advanced glycation endproducts formation by Korean thistle, Cirsium maackii","volume":"8","author":"Jung","year":"2015","journal-title":"Asian Pac. J. Trop. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1016\/j.fct.2009.08.014","article-title":"Quantitative HPLC analysis of two key flavonoids and inhibitory activities against aldose reductase from different parts of the Korean thistle, Cirsium maackii","volume":"47","author":"Jung","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s13765-017-0302-z","article-title":"Determination of flavonoids from Cirsium japonicum var. maackii and their inhibitory activities against aldose reductase","volume":"60","author":"Lee","year":"2017","journal-title":"Appl. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrneurol.2010.130","article-title":"How does diabetes accelerate Alzheimer disease pathology?","volume":"6","author":"Kim","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jns.2007.01.017","article-title":"Brain mitochondrial dysfunction as a link between Alzheimer\u2019s disease and diabetes","volume":"257","author":"Moreira","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3233\/JAD-2001-3111","article-title":"Alzheimer\u2019s disease results from the cerebral accumulation and cytotoxicity of amyloid \u03b2-protein","volume":"3","author":"Selkoe","year":"2001","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2165\/00023210-200317010-00003","article-title":"The role of insulin resistance in the pathogenesis of Alzheimer\u2019s disease","volume":"17","author":"Watson","year":"2003","journal-title":"CNS Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.apjtm.2017.10.018","article-title":"Comparative molecular docking studies of lupeol and lupenone isolated from Pueraria lobata that inhibits BACE1: Probable remedies for Alzheimer\u2019s disease","volume":"10","author":"Koirala","year":"2017","journal-title":"Asian Pac. J. Trop. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/bmb.20243","article-title":"A qualitative approach to enzyme inhibition","volume":"37","author":"Waldrop","year":"2009","journal-title":"Biochem. Mol. Biol. Educ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.foodchem.2012.05.104","article-title":"Isolation and identification of phenolic compounds from the seeds of Perilla frutescens (L.) and their inhibitory activities against \u03b1-glucosidase and aldose reductase","volume":"135","author":"Ha","year":"2012","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ijbiomac.2013.12.007","article-title":"\u03b1-Glucosidase inhibition by luteolin: Kinetics, interaction and molecular docking","volume":"64","author":"Yan","year":"2014","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.jasms.2009.04.003","article-title":"Screening and structural characterization of \u03b1-glucosidase inhibitors from hawthorn leaf flavonoids extract by ultrafiltration LC-DAD-MSn and SORI-CID FTICR MS","volume":"20","author":"Li","year":"2009","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3177\/jnsv.52.149","article-title":"Inhibition of \u03b1-glucosidase and \u03b1-amylase by flavonoids","volume":"52","author":"Tadera","year":"2006","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1271\/bbb.64.2458","article-title":"Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid","volume":"64","author":"Kim","year":"2000","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_33","first-page":"471","article-title":"Chemical constituents of the aerial parts of Scutellaria lateriflora and their alpha-glucosidase inhibitory activities","volume":"7","author":"Kuroda","year":"2012","journal-title":"Nat. Prod. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1080\/14756366.2017.1368503","article-title":"\u03b1-Glucosidase inhibition by flavonoids: An in vitro and in silico structure\u2013activity relationship study","volume":"32","author":"Freitas","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.2174\/092986610792231492","article-title":"Inhibition kinetics of flavonoids on yeast \u03b1-glucosidase merged with docking simulations","volume":"17","author":"Xu","year":"2010","journal-title":"Protein Pept. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12272-001-1139-9","article-title":"\u03b2-Secretase (BACE1) inhibitors from Perilla frutescens var. acuta","volume":"31","author":"Choi","year":"2008","journal-title":"Arch. Pharmacal Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.neuroscience.2009.05.009","article-title":"The anti-amnesic effects of luteolin against amyloid \u03b225\u201335 peptide-induced toxicity in mice involve the protection of neurovascular unit","volume":"162","author":"Liu","year":"2009","journal-title":"Neuroscience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1582-4934.2008.00344.x","article-title":"Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer\u2019s disease \u03b2-amyloid production","volume":"13","author":"Bai","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1142\/S0192415X10007841","article-title":"The ameliorating effects of luteolin on beta-amyloid-induced impairment of water maze performance and passive avoidance in rats","volume":"38","author":"Tsai","year":"2010","journal-title":"Am. J. Chin. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1002\/ptr.2940","article-title":"Neuroprotective effect of luteolin on amyloid \u03b2 protein (25\u201335)-induced toxicity in cultured rat cortical neurons","volume":"24","author":"Cheng","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/jps.1031","article-title":"Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure\u2013activity relationship (QSAR) with the Abraham descriptors","volume":"90","author":"Zhao","year":"2001","journal-title":"J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1023\/A:1012102522787","article-title":"In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man\u2014Fact or myth","volume":"14","author":"Yee","year":"1997","journal-title":"Pharm. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0928-0987(00)00076-2","article-title":"Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells","volume":"10","author":"Yamashita","year":"2000","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1021\/js9803205","article-title":"MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening","volume":"88","author":"Irvine","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0014-5793(98)01304-0","article-title":"Intestinal absorption of luteolin and luteolin 7-O-\u03b2-glucoside in rats and humans","volume":"438","author":"Shimoi","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0014-5793(99)01160-6","article-title":"The small intestine can both absorb and glucuronidate luminal flavonoids","volume":"458","author":"Spencer","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1021\/acs.jafc.6b00964","article-title":"Metabolic fate of luteolin in rats: Its relationship to anti-inflammatory effect","volume":"64","author":"Kure","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7693","DOI":"10.1021\/acs.jafc.5b00232","article-title":"Absorption and metabolism of luteolin and its glycosides from the extract of Chrysanthemum morifolium flowers in rats and Caco-2 cells","volume":"63","author":"Yasuda","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sl\u00e1mov\u00e1, K., Kape\u0161ov\u00e1, J., and Valentov\u00e1, K. (2018). \u201cSweet flavonoids\u201d: Glycosidase-catalyzed modifications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072126"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"17236","DOI":"10.1021\/acsomega.8b02694","article-title":"Discovery of a highly potent tyrosinase inhibitor, luteolin 5-O-\u03b2-d-glucopyranoside, isolated from Cirsium japonicum var. maakii (Maxim.) Matsum., Korean thistle: Kinetics and computational molecular docking simulation","volume":"3","author":"Wagle","year":"2018","journal-title":"ACS Omega"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Agrawal, P.K. (1989). Carbon-13 NMR of Flavonoids, Elsevier Science Publishers.","DOI":"10.1016\/B978-0-444-87449-8.50011-0"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/BF02856534","article-title":"Hypoglycemic and hypolipemic effects of Ixeris dentata in diabetic rats","volume":"13","author":"Choi","year":"1990","journal-title":"Arch. Pharm. Res."},{"key":"ref_53","first-page":"1128","article-title":"A microplate based screening method for \u03b1-glucosidase inhibitors","volume":"10","author":"Li","year":"2005","journal-title":"Chin. J. Clin. Pharm. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.bmcl.2005.11.071","article-title":"Protein tyrosine phosphatase 1B inhibitors from Morus root bark","volume":"16","author":"Cui","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.fct.2016.01.014","article-title":"Kinetics and molecular docking studies of fucosterol and fucoxanthin, BACE1 inhibitors from brown algae Undaria pinnatifida and Ecklonia stolonifera","volume":"89","author":"Jung","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0308-8146(00)00108-4","article-title":"Antioxidant activity of anthraquinones and anthrone","volume":"70","author":"Yen","year":"2000","journal-title":"Food Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Paudel, P., Jung, H.A., and Choi, J.S. (2018). Anthraquinone and naphthopyrone glycosides from Cassia obtusifolia seeds mediate hepatoprotection via Nrf2-mediated HO-1 activation and MAPK modulation. Arch. Pharmacal Res., 1\u201313.","DOI":"10.1007\/s12272-018-1040-4"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/1811199a0","article-title":"Antioxidant determinations by the use of a stable free radical","volume":"181","author":"Blois","year":"1958","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0891-5849(94)90138-4","article-title":"Peroxynitrite-mediated oxidation of dihydrorhodamine 123","volume":"16","author":"Kooy","year":"1994","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1021\/ja01318a036","article-title":"The determination of enzyme dissociation constants","volume":"56","author":"Lineweaver","year":"1934","journal-title":"J. Am. Chem. Soc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1042\/bj1370143","article-title":"A simple graphical method for determining the inhibition constants of mixed, uncompetitive and noncompetitive inhibitors","volume":"137","year":"1974","journal-title":"Biochem. J."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/3\/649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:31:28Z","timestamp":1760185888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/3\/649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,12]]},"references-count":61,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["molecules24030649"],"URL":"https:\/\/doi.org\/10.3390\/molecules24030649","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,12]]}}}