{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T07:03:45Z","timestamp":1776495825597,"version":"3.51.2"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Czech Science Foundation 18-00150S","award":["18-00150S"],"award-info":[{"award-number":["18-00150S"]}]},{"name":"MEYS LTC","award":["17009"],"award-info":[{"award-number":["17009"]}]},{"name":"NMTrypI \u2013 New Medicines for Trypanosomatidic Infections","award":["grant agreement n\u00ba 603240"],"award-info":[{"award-number":["grant agreement n\u00ba 603240"]}]},{"DOI":"10.13039\/501100000921","name":"COST","doi-asserted-by":"publisher","award":["Action CM1307"],"award-info":[{"award-number":["Action CM1307"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Flavonolignans from the seeds of the milk thistle (Silybum marianum) have been extensively used in folk medicine for centuries. Confirmation of their properties as hepatoprotective, antioxidant and anticancer has been obtained using standardized extracts and purified flavonolignans. Information on their potential effect on Leishmania is very scarce. We have investigated the effect of silymarin, silybin and related flavonolignans on the multiplication of promastigotes in vitro and ex vivo on intracellular amastigotes of L. infantum (Li) and L. donovani (Ld), causative agents of human and canine visceral leishmaniasis (VL). In addition, the potential synergistic effect of the most active molecule and well-established antileishmanial drugs against promastigotes was explored. Dehydroisosilybin A elicited the highest inhibition against Ld and Li promastigotes with an approximate IC50 of 90.23 \u00b5M. This molecule showed a moderate synergism with amphotericin B (AmB) but not with SbIII or paromomycin, although it was ineffective against amastigotes. Antileishmanial activity on intracellular amastigotes of the two diastereoisomers of dehydrosilybin (10 \u00b5M) was comparable to that elicited by 0.1 \u00b5M AmB. Antiproliferative activity and safety of flavonolignans suggest the interest of exploring their potential value in combination therapy against VL.<\/jats:p>","DOI":"10.3390\/molecules23071560","type":"journal-article","created":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T11:02:05Z","timestamp":1530097325000},"page":"1560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In-Vitro Activity of Silybin and Related Flavonolignans against Leishmania infantum and L. donovani"],"prefix":"10.3390","volume":"23","author":[{"given":"Ana Isabel","family":"Ol\u00edas-Molero","sequence":"first","affiliation":[{"name":"Department of Animal Health, Research Group ICPVet, Faculty of Veterinary Medicine, University Complutense, Avda. Puerta de Hierro s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Dolores","family":"Jim\u00e9nez-Ant\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Animal Health, Research Group ICPVet, Faculty of Veterinary Medicine, University Complutense, Avda. Puerta de Hierro s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-9301","authenticated-orcid":false,"given":"David","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Institute of Microbiology of the Czech Academy of Sciences, Laboratory of Biotransformation, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda J.","family":"Corral","sequence":"additional","affiliation":[{"name":"Department of Animal Health, Research Group ICPVet, Faculty of Veterinary Medicine, University Complutense, Avda. Puerta de Hierro s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Alunda","sequence":"additional","affiliation":[{"name":"Department of Animal Health, Research Group ICPVet, Faculty of Veterinary Medicine, University Complutense, Avda. Puerta de Hierro s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,27]]},"reference":[{"key":"ref_1","unstructured":"(2018, April 04). DNDi. Available online: https:\/\/www.dndi.org\/diseases-projects\/leishmaniasis\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"588","DOI":"10.3855\/jidc.6833","article-title":"Recent updates and perspectives on leishmaniasis","volume":"9","author":"Savoia","year":"2015","journal-title":"J. Infect. Dev. Ctries"},{"key":"ref_3","unstructured":"(2018, April 04). World Health Organization (WHO). Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs375\/en\/2015."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.ijid.2010.06.019","article-title":"Leishmaniasis, an emerging infection in travelers","volume":"14","author":"Pavli","year":"2010","journal-title":"Int. J. Infect. 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