{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T10:10:07Z","timestamp":1776766207014,"version":"3.51.2"},"reference-count":54,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["(No. 18-00121S)."],"award-info":[{"award-number":["(No. 18-00121S)."]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Charles University","doi-asserted-by":"publisher","award":["SVV 2020\/260 414"],"award-info":[{"award-number":["SVV 2020\/260 414"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education, Youth and Sport, Czech Republic","award":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000841"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000841"]}]},{"name":"Ministry of Education, Youth and Sport, Czech Republic","award":["CZ.02.1.01\/0.0\/0.0\/16_017\/0002682"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_017\/0002682"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Silymarin is known for its hepatoprotective effects. Although there is solid evidence for its protective effects against Amanita phalloides intoxication, only inconclusive data are available for alcoholic liver damage. Since silymarin flavonolignans have metal-chelating activity, we hypothesized that silymarin may influence alcoholic liver damage by inhibiting zinc-containing alcohol dehydrogenase (ADH). Therefore, we tested the zinc-chelating activity of pure silymarin flavonolignans and their effect on yeast and equine ADH. The most active compounds were also tested on bovine glutamate dehydrogenase, an enzyme blocked by zinc ions. Of the six flavonolignans tested, only 2,3-dehydroderivatives (2,3-dehydrosilybin and 2,3-dehydrosilychristin) significantly chelated zinc ions. Their effect on yeast ADH was modest but stronger than that of the clinically used ADH inhibitor fomepizole. In contrast, fomepizole strongly blocked mammalian (equine) ADH. 2,3-Dehydrosilybin at low micromolar concentrations also partially inhibited this enzyme. These results were confirmed by in silico docking of active dehydroflavonolignans with equine ADH. Glutamate dehydrogenase activity was decreased by zinc ions in a concentration-dependent manner, and this inhibition was abolished by a standard zinc chelating agent. In contrast, 2,3-dehydroflavonolignans blocked the enzyme both in the absence and presence of zinc ions. Therefore, 2,3-dehydrosilybin might have a biologically relevant inhibitory effect on ADH and glutamate dehydrogenase.<\/jats:p>","DOI":"10.3390\/nu13124238","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:56Z","timestamp":1638314576000},"page":"4238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Silymarin Dehydroflavonolignans Chelate Zinc and Partially Inhibit Alcohol Dehydrogenase"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7116-0333","authenticated-orcid":false,"given":"V\u00e1clav","family":"Tvrd\u00fd","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Heyrovsk\u00e9ho 1203, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-9366","authenticated-orcid":false,"given":"Marcel","family":"Hrub\u0161a","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Heyrovsk\u00e9ho 1203, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Jirkovsk\u00fd","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Heyrovsk\u00e9ho 1203, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-9301","authenticated-orcid":false,"given":"David","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Kut\u00fd","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of South Bohemia in Ceske Budejovice, Branisovska 1760, 370 05 Ceske Budejovice, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7714-5350","authenticated-orcid":false,"given":"Kate\u0159ina","family":"Valentov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-4020","authenticated-orcid":false,"given":"Vladim\u00edr","family":"K\u0159en","sequence":"additional","affiliation":[{"name":"Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-6900","authenticated-orcid":false,"given":"P\u0159emysl","family":"Mlad\u011bnka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Heyrovsk\u00e9ho 1203, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.foodres.2017.07.017","article-title":"The silymarin composition\u2026 and why does it matter?","volume":"100","author":"Chambers","year":"2017","journal-title":"Food Res. 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