{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:57:49Z","timestamp":1792803469479,"version":"4.5.0"},"reference-count":98,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o","award":["FAPEMA\/CAPES ACT-05691\/21"],"award-info":[{"award-number":["FAPEMA\/CAPES ACT-05691\/21"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o","award":["ACT-01784\/21"],"award-info":[{"award-number":["ACT-01784\/21"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o","award":["317186\/2023-0"],"award-info":[{"award-number":["317186\/2023-0"]}]},{"name":"FAPEMA\u2014Foundation for Research and Scientific and Technological Development Support of Maranh\u00e3o","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]},{"name":"CAPES-Coordination for the Improvement of Higher Education Personnel","award":["FAPEMA\/CAPES ACT-05691\/21"],"award-info":[{"award-number":["FAPEMA\/CAPES ACT-05691\/21"]}]},{"name":"CAPES-Coordination for the Improvement of Higher Education Personnel","award":["ACT-01784\/21"],"award-info":[{"award-number":["ACT-01784\/21"]}]},{"name":"CAPES-Coordination for the Improvement of Higher Education Personnel","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"CAPES-Coordination for the Improvement of Higher Education Personnel","award":["317186\/2023-0"],"award-info":[{"award-number":["317186\/2023-0"]}]},{"name":"CAPES-Coordination for the Improvement of Higher Education Personnel","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["FAPEMA\/CAPES ACT-05691\/21"],"award-info":[{"award-number":["FAPEMA\/CAPES ACT-05691\/21"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["ACT-01784\/21"],"award-info":[{"award-number":["ACT-01784\/21"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["317186\/2023-0"],"award-info":[{"award-number":["317186\/2023-0"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CNPq\u2014National Council for Scientific and Technological Development","award":["309098\/2023-8"],"award-info":[{"award-number":["309098\/2023-8"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Silybin, a flavonolignan extracted from the seeds of the plant species Silybum marianum (L.) Gaertn., has a variety of pharmacological activities, including antimicrobial activity against several microorganisms of clinical interest. This review analyzes the existing studies on silybin\u2019s antimicrobial activity and possible mechanisms of action. Silybin has been shown to inhibit the growth of Gram-positive and Gram-negative bacteria, as well as some fungi, viruses, and protozoa. In general, possible mechanisms of antimicrobial action include the inhibition of efflux pumps, prevention of biofilm formation, reduction of the expression of virulence factors, induction of apoptosis-like effects, and plasma membrane damage, as well as the inhibition of nucleic acid and protein synthesis. Silybin has been shown to have synergistic effects when combined with conventional antibiotics against both drug-sensitive and drug-resistant microorganisms. However, the low bioavailability observed for this flavonolignan has been a challenge to its clinical use. In this context, nanotechnology has been used to increase silybin\u2019s bioavailability while enhancing its antimicrobial activity. Furthermore, certain structural modifications have been able to enhance its antimicrobial activity in comparison to that of the natural molecule. Overall, this review provides insights into the scientific understanding of the mechanism of action of silybin and its desired properties for the effective treatment of infections.<\/jats:p>","DOI":"10.3390\/antibiotics13111091","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T05:33:04Z","timestamp":1731648784000},"page":"1091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Comprehensive Review on the Antibacterial, Antifungal, Antiviral, and Antiparasitic Potential of Silybin"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-3831","authenticated-orcid":false,"given":"Jos\u00e9 Lima","family":"Pereira-Filho","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-996X","authenticated-orcid":false,"given":"Amanda Graziela Gon\u00e7alves","family":"Mendes","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-0662","authenticated-orcid":false,"given":"Carmem Duarte Lima","family":"Campos","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2083-0589","authenticated-orcid":false,"given":"Israel Viegas","family":"Moreira","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7974-4237","authenticated-orcid":false,"given":"Cinara Regina Arag\u00e3o Vieira","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-3920","authenticated-orcid":false,"given":"Suzany Hellen da Silva","family":"Soczek","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Curitiba 80250-060, PR, Brazil"},{"name":"Faculdades Pequeno Pr\u00edncipe, Curitiba 80250-060, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-2514","authenticated-orcid":false,"given":"Elizabeth Soares","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Curitiba 80250-060, PR, Brazil"},{"name":"Faculdades Pequeno Pr\u00edncipe, Curitiba 80250-060, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-8308","authenticated-orcid":false,"given":"Rafael Cardoso","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2868-1314","authenticated-orcid":false,"given":"Val\u00e9rio","family":"Monteiro-Neto","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/22221751.2022.2030196","article-title":"Antibiotic resistance in hospital-acquired ESKAPE-E infections in low-and lower-middle-income countries: A systematic review and meta-analysis","volume":"11","author":"Ayobami","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_2","first-page":"173","article-title":"Multidrug-resistant microbial therapy using antimicrobial peptides and the CRISPR\/Cas9 system","volume":"13","author":"Getahun","year":"2022","journal-title":"Vet. Med. Res. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dar, M.A., Gul, R., Karuppiah, P., Al-Dhabi, N.A., and Alfadda, A.A. (2022). Antibacterial activity of cerium oxide nanoparticles against ESKAPE pathogens. Crystals, 12.","DOI":"10.3390\/cryst12020179"},{"key":"ref_4","first-page":"743","article-title":"Antimicrobial resistance: One health approach","volume":"15","year":"2022","journal-title":"Vet. World"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"735","DOI":"10.2147\/IDR.S345574","article-title":"Clinical perspective of antimicrobial resistance in bacteria","volume":"15","author":"Zhu","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Monteiro-Neto, V., de Souza, C.D., Gonzaga, L.F., da Silveira, B.C., Sousa, N.C., Pontes, J.P., Santos, D.M., Martins, W.C., Pessoa, J.F., and Carvalho Junior, A.R. (2020). Cuminaldehyde potentiates the antimicrobial actions of ciprofloxacin against Staphylococcus aureus and Escherichia coli. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232987"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tak\u00f3, M., Kerekes, E.B., Zambrano, C., Kotog\u00e1n, A., Papp, T., Krisch, J., and V\u00e1gv\u00f6lgyi, C. (2020). Plant phenolics and phenolic-enriched extracts as antimicrobial agents against food-contaminating microorganisms. Antioxidants, 9.","DOI":"10.3390\/antiox9020165"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Donadio, G., Mensitieri, F., Santoro, V., Parisi, V., Bellone, M.L., De Tommasi, N., Izzo, V., and Dal Piaz, F. (2021). Interactions with microbial proteins driving the antibacterial activity of flavonoids. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050660"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hurtov\u00e1, M., K\u00e1\u0148ov\u00e1, K., Dobiasov\u00e1, S., Holasov\u00e1, K., \u010c\u00e1kov\u00e1, D., Hoang, L., Biedermann, D., Kuzma, M., Cva\u010dka, J., and K\u0159en, V. (2022). Selectively halogenated flavonolignans\u2014Preparation and antibacterial activity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315121"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1021\/np900758d","article-title":"Enzymatic kinetic resolution of silybin diastereoisomers","volume":"73","author":"Monti","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/iub.1647","article-title":"Assessment of silibinin as a potential antifungal agent and investigation of its mechanism of action","volume":"69","author":"Yun","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117977","DOI":"10.1016\/j.lfs.2020.117977","article-title":"The gastroprotective potential of silibinin against Helicobacter pylori infection and gastric tumor cells","volume":"256","author":"Bittencourt","year":"2020","journal-title":"Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Verdura, S., Cuy\u00e0s, E., Ruiz-Torres, V., Micol, V., Joven, J., Bosch-Barrera, J., and Menendez, J.A. (2021). Lung cancer management with silibinin: A historical and translational perspective. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060559"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rakelly de Oliveira, D., Relison Tintino, S., Morais Braga, M.F.B., Boligon, A.A., Linde Athayde, M., Douglas Melo Coutinho, H., de Menezes, I.R.A., and Fachinetto, R. (2015). In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/292797"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Alhadrami, H.A., Hamed, A.A., Hassan, H.M., Belbahri, L., Rateb, M.E., and Sayed, A.M. (2020). Flavonoids as potential anti-MRSA agents through modulation of PBP2a: A computational and experimental study. Antibiotics, 9.","DOI":"10.3390\/antibiotics9090562"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, C., Sui, Y., Liu, S., and Yang, M. (2023). Anti-viral activity of bioactive molecules of silymarin against COVID-19 via in silico studies. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101479"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3347\/PHD.23078","article-title":"Antiamoebic activities of flavonoids against pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba species","volume":"61","author":"Kang","year":"2023","journal-title":"Parasites Hosts Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fallah, M., Davoodvandi, A., Nikmanzar, S., Aghili, S., Mirazimi, S.M.A., Aschner, M., Rashidian, A., Hamblin, M.R., Chamanara, M., and Naghsh, N. (2021). Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomed. Pharmacother., 142.","DOI":"10.1016\/j.biopha.2021.112024"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1016\/S0040-4039(00)89610-0","article-title":"The structure of silybin (silybum substance E6), the first flavonolignan","volume":"9","author":"Pelter","year":"1968","journal-title":"Tetrahedron Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/cber.19751080312","article-title":"Structure of silybin. 1. Degradative experiments","volume":"108","author":"Pelter","year":"1975","journal-title":"Chem. Berichte-Recl."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bijak, M. (2017). Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.)\u2014Chemistry, bioavailability, and metabolism. Molecules, 22.","DOI":"10.3390\/molecules22111942"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1039\/C3NP70122K","article-title":"Chemistry of silybin","volume":"31","author":"Biedermann","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"K\u0159en, V. (2021). Chirality Matters: Biological activity of optically pure silybin and its congeners. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157885"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hao, Y., Wei, Z., Wang, Z., Li, G., Yao, Y., and Dun, B. (2021). Biotransformation of flavonoids improves antimicrobial and anti-breast cancer activities in vitro. Foods, 10.","DOI":"10.3390\/foods10102367"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.26444\/aaem\/161220","article-title":"Antimicrobial synergistic effects of apigenin, (-)-epigallocatechin-3-gallate, myricetin and luteolin in combination with some antibiotics","volume":"30","author":"Hanci","year":"2023","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_26","first-page":"827","article-title":"Inhibitory effects of silybin on the efflux pump of methicillin-resistant Staphylococcus aureus","volume":"18","author":"Wang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1007\/s12275-008-0138-7","article-title":"Synergistic antibacterial effect between silybin and N, N\u2032-dicyclohexylcarbodiimide in clinical Pseudomonas aeruginosa isolates","volume":"46","author":"Jung","year":"2008","journal-title":"J. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3109\/13880209.2010.519390","article-title":"Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids","volume":"49","author":"Kartal","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.2147\/DDDT.S133806","article-title":"Fabrication, characterization and in vitro evaluation of silibinin nanoparticles: An attempt to enhance its oral bioavailability","volume":"11","author":"Sahibzada","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.biopha.2018.03.133","article-title":"Concentration-dependent dual effects of silibinin on kanamycin-induced cells death in Staphylococcus aureus","volume":"102","author":"Cai","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","first-page":"920","article-title":"Improvement of the functionality of pancreatic Langerhans islets via reduction of bacterial contamination and apoptosis using phenolic compounds","volume":"21","author":"Rahimifard","year":"2018","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.colsurfb.2018.04.007","article-title":"Synthesis and characterization of zinc-silibinin complexes: A potential bioactive compound with angiogenic, and antibacterial activity for bone tissue engineering","volume":"167","author":"Vimalraj","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1021\/np990639k","article-title":"5\u2032-Methoxyhydnocarpin-D and Pheophorbide a: Berberis species components that potentiate Berberine growth inhibition of resistant Staphylococcus aureus","volume":"63","author":"Stermitz","year":"2000","journal-title":"J. Nat. Prod."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Holasov\u00e1, K., K\u0159\u00ed\u017ekovsk\u00e1, B., Hoang, L., Dobiasova, S., Lipov, J., Macek, T., K\u0159en, V., Valentov\u00e1, K., Ruml, T., and Viktorova, J. (2022). Flavonolignans from silymarin modulate antibiotic resistance and virulence in Staphylococcus aureus. Biomed. Pharmacother., 149.","DOI":"10.1016\/j.biopha.2022.112806"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lee, Y.-S., Jang, K.-A., and Cha, J.-D. (2012). Synergistic antibacterial effect between silibinin and antibiotics in oral bacteria. Biomed. Res. Int., 2012.","DOI":"10.1155\/2012\/618081"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.4014\/jmb.1710.10029","article-title":"Reactive oxygen species depletion by silibinin stimulates apoptosis-like death in Escherichia coli","volume":"27","author":"Lee","year":"2017","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101181","DOI":"10.1016\/j.jddst.2019.101181","article-title":"Silybin-conjugated gold nanoparticles for antimicrobial chemotherapy against Gram-negative bacteria","volume":"53","author":"Islan","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1080\/09205063.2024.2355744","article-title":"Silibinin-loaded chitosan-capped silver nanoparticles exhibit potent antimicrobial, antibiofilm, and anti-inflammatory activity against drug-resistant nosocomial pathogens","volume":"35","author":"Chand","year":"2024","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Fekri Kohan, S., Nouhi Kararoudi, A., Bazgosha, M., Adelifar, S., Hafezolghorani Esfahani, A., Ghaderi Barmi, F., Kouchakinejad, R., Barzegari, E., Shahriarinour, M., and Ranji, N. (2024). Determining the potential targets of silybin by molecular docking and its antibacterial functions on efflux pumps and porins in uropathogenic E. coli. Int. Microbiol., 1\u201312.","DOI":"10.1007\/s10123-024-00488-9"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Omer, F.H., Al-Khafaji, N.S., Al-Alaq, F.T., Al-Dahmoshi, H.O., Memariani, M., and Saki, M. (2022). Synergistic effects of silybin and curcumin on virulence and carbapenemase genes expression in multidrug resistant Klebsiella oxytoca. BMC Res. Notes, 15.","DOI":"10.1186\/s13104-022-06172-3"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/BF02976707","article-title":"Gram-positive bacteria specific properties of silybin derived from Silybum marianum","volume":"26","author":"Lee","year":"2003","journal-title":"Arch. Pharmacal Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Flores, E.M., Mata-Espinosa, D., Barrios-Payan, J., Marquina-Castillo, B., Casta\u00f1\u00f3n-Arreola, M., and Hern\u00e1ndez-Pando, R. (2019). A significant therapeutic effect of silymarin administered alone, or in combination with chemotherapy, in experimental pulmonary tuberculosis caused by drug-sensitive or drug-resistant strains: In vitro and in vivo studies. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217457"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1002\/biot.201000422","article-title":"Synergistic effects between silibinin and antibiotics on methicillin-resistant Staphylococcus aureus isolated from clinical specimens","volume":"6","author":"Kang","year":"2011","journal-title":"Biotechnol. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/jam.14149","article-title":"Silibinin attenuates Streptococcus suis serotype 2 virulence by targeting suilysin","volume":"126","author":"Shen","year":"2019","journal-title":"J. Appl. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s11694-016-9456-3","article-title":"Antioxidant activity and antimicrobial effect of tarragon (Artemisia dracunculus) extract and chemical composition of its essential oil","volume":"11","author":"Behbahani","year":"2017","journal-title":"J. Food Meas. Charact."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1016\/j.arabjc.2020.01.002","article-title":"Enhancement of bioavailability and hepatoprotection by silibinin through conversion to nanoparticles prepared by liquid antisolvent method","volume":"13","author":"Sahibzada","year":"2020","journal-title":"Arab. J. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biocel.2016.09.008","article-title":"Silibinin triggers yeast apoptosis related to mitochondrial Ca2+ influx in Candida albicans","volume":"80","author":"Yun","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"789","DOI":"10.5530\/pj.2018.4.133","article-title":"In vitro antifungal effects of hesperetin and silibinin","volume":"10","author":"Gowtham","year":"2018","journal-title":"Pharmacogn. J."},{"key":"ref_49","first-page":"20","article-title":"Inhibitory effect of silibinin on hepatitis B virus entry","volume":"14","author":"Umetsu","year":"2018","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1053\/j.gastro.2008.07.072","article-title":"Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon\/ribavirin therapy","volume":"135","author":"Ferenci","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1053\/j.gastro.2009.11.053","article-title":"Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase","volume":"138","author":"Ahnou","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jcv.2010.07.006","article-title":"Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV\u2013HCV coinfected patient","volume":"49","author":"Payer","year":"2010","journal-title":"J. Clin. Virol."},{"key":"ref_53","first-page":"1","article-title":"Treatment of hepatitis C-virus-reinfection after liver transplant with silibinin in nonresponders to pegylated interferon-based therapy","volume":"9","author":"Eurich","year":"2011","journal-title":"Exp. Clin. Transplant. Off. J. Middle East Soc. Organ Transplant."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wagoner, J., Morishima, C., Graf, T.N., Oberlies, N.H., Teissier, E., P\u00e9cheur, E.-I., Tavis, J.E., and Polyak, S.J. (2011). Differential in vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016464"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"411","DOI":"10.5812\/hepatmon.6135","article-title":"Failure of intravenous silibinin monotherapy to prevent hepatitis C genotype 2A liver graft reinfection","volume":"12","author":"Aghemo","year":"2012","journal-title":"Hepat. Mon."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.jhep.2011.12.012","article-title":"Understanding silibinin\u2019s modes of action against HCV using viral kinetic modeling","volume":"56","author":"Guedj","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_57","first-page":"1866","article-title":"Silibinin inhibits hepatitis C virus entry into hepatocytes by hindering clathrin-dependent trafficking","volume":"15","author":"Blaising","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jhep.2012.09.034","article-title":"Intravenous silibinin monotherapy shows significant antiviral activity in HCV-infected patients in the peri-transplantation period","volume":"58","author":"Crespo","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/hep.26260","article-title":"Analysis of hepatitis C virus resistance to silibinin in vitro and in vivo points to a novel mechanism involving nonstructural protein 4B","volume":"57","author":"Ganten","year":"2013","journal-title":"Hepatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/hiv.12166","article-title":"Efficacy of lead-in silibinin and subsequent triple therapy in difficult-to-treat HIV\/hepatitis C virus-coinfected patients","volume":"15","author":"Braun","year":"2014","journal-title":"HIV Med."},{"key":"ref_61","first-page":"159","article-title":"In silico studies of medicinal compounds against hepatitis C capsid protein from north India","volume":"8","year":"2014","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/tri.12324","article-title":"Antiviral activity and safety profile of silibinin in HCV patients with advanced fibrosis after liver transplantation: A randomized clinical trial","volume":"27","author":"Rendina","year":"2014","journal-title":"Transpl. Int."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Braun, D.L., Rauch, A., Aouri, M., Durisch, N., Eberhard, N., Anagnostopoulos, A., Ledergerber, B., M\u00fcllhaupt, B., Metzner, K.J., and Decosterd, L. (2015). A lead-in with silibinin prior to triple-therapy translates into favorable treatment outcomes in difficult-to-treat HIV\/hepatitis C coinfected patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133028"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3851\/IMP2806","article-title":"Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy","volume":"20","author":"Canini","year":"2015","journal-title":"Antivir. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/liv.12692","article-title":"Sustained virological response with intravenous silibinin: Individualized IFN-free therapy via real-time modelling of HCV kinetics","volume":"35","author":"Dahari","year":"2015","journal-title":"Liver Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13737-016-0030-7","article-title":"Immunomodulating effects of the anti-viral agent Silibinin in liver transplant patients with HCV recurrence","volume":"5","author":"Castellaneta","year":"2016","journal-title":"Transplant. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.antiviral.2015.10.008","article-title":"Assessment of the activity of directly acting antivirals and other products against different genotypes of hepatitis C virus prevalent in resource-poor countries","volume":"125","author":"Khan","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Malaguarnera, G., Bertino, G., Chisari, G., Motta, M., Vecchio, M., Vacante, M., Caraci, F., Greco, C., Drago, F., and Nunnari, G. (2016). Silybin supplementation during HCV therapy with pegylated interferon-\u03b1 plus ribavirin reduces depression and anxiety and increases work ability. BMC Psychiatry, 16.","DOI":"10.1186\/s12888-016-1115-z"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1136\/gutjnl-2016-312019","article-title":"Highly bioavailable silibinin nanoparticles inhibit HCV infection","volume":"66","author":"Liu","year":"2017","journal-title":"Gut"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Cossiga, V., Sanduzzi-Zamparelli, M., Sapena, V., Guarino, M., Dallio, M., Torrisi, E., Pignata, L., Federico, A., Salomone, F., and Morisco, F. (2022). Beneficial Effects of Silybin Treatment After Viral Eradication in Patients with HCV-Related Advanced Chronic Liver Disease: A Pilot Study. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.824879"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"McClure, J., Lovelace, E.S., Elahi, S., Maurice, N.J., Wagoner, J., Dragavon, J., Mittler, J.E., Kraft, Z., Stamatatos, L., and Horton, H. (2012). Silibinin inhibits HIV-1 infection by reducing cellular activation and proliferation. PLoS ONE, 7.","DOI":"10.1371\/annotation\/78ba072a-6b7a-430a-8fcd-ef020e4fc458"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.bioorg.2018.01.026","article-title":"Silibinin phosphodiester glyco-conjugates: Synthesis, redox behaviour and biological investigations","volume":"77","author":"Romanucci","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1128\/AAC.00759-13","article-title":"Identification of 23-(s)-2-amino-3-phenylpropanoyl-silybin as an antiviral agent for influenza A virus infection in vitro and in vivo","volume":"57","author":"Dai","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s11626-022-00666-x","article-title":"In silico and in vitro evaluation of silibinin: A promising anti-Chikungunya agent","volume":"58","author":"Dutta","year":"2022","journal-title":"In Vitr. Cell. Dev. Biol.-Anim."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"153977","DOI":"10.1016\/j.phymed.2022.153977","article-title":"Inhibitory effect of tanshinone IIA, resveratrol and silibinin on enterovirus 68 production through inhibiting ATM and DNA-PK pathway","volume":"99","author":"Su","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bosch-Barrera, J., Martin-Castillo, B., Bux\u00f3, M., Brunet, J., Encinar, J.A., and Menendez, J.A. (2020). Silibinin and SARS-CoV-2: Dual targeting of host cytokine storm and virus replication machinery for clinical management of COVID-19 patients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061770"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Sardanelli, A.M., Isgr\u00f2, C., and Palese, L.L. (2021). SARS-CoV-2 main protease active site ligands in the human metabolome. Molecules, 26.","DOI":"10.3390\/molecules26051409"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1002\/ptr.7107","article-title":"Silibinin as potential tool against SARS-CoV-2: In silico spike receptor-binding domain and main protease molecular docking analysis, and in vitro endothelial protective effects","volume":"35","author":"Speciale","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1002\/ptr.7486","article-title":"Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS-CoV-2","volume":"36","author":"Hamdy","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s001090000169","article-title":"Identification and characterization of trypanocides by functional expression of an adenosine transporter from Trypanosoma brucei in yeast","volume":"79","author":"Vogel","year":"2001","journal-title":"J. Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1007\/s00436-020-06944-5","article-title":"Evaluation of the anti-Trypanosoma cruzi activity in vitro and in vivo of silibinin and silibinin in association to benznidazole","volume":"120","author":"Torchelsen","year":"2021","journal-title":"Parasitol. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1128\/AAC.45.2.439-446.2001","article-title":"High-affinity binding of silybin derivatives to the nucleotide-binding domain of a Leishmania tropica P-glycoprotein-like transporter and chemosensitization of a multidrug-resistant parasite to daunomycin","volume":"45","author":"Conseil","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Sharma, M., Sehgal, R., and Kaur, S. (2012). Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. PLoS Neglected Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001629"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Ol\u00edas-Molero, A.I., Jim\u00e9nez-Ant\u00f3n, M.D., Biedermann, D., Corral, M.J., and Alunda, J.M. (2018). In-vitro activity of silybin and related flavonolignans against Leishmania infantum and L. donovani. Molecules, 23.","DOI":"10.3390\/molecules23071560"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Hr\u010dkov\u00e1, G., Kuba\u0161kov\u00e1, T.M., Benada, O., Kofro\u0148ov\u00e1, O., Tumov\u00e1, L., and Biedermann, D. (2018). Differential effects of the flavonolignans silybin, silychristin and 2, 3-dehydrosilybin on Mesocestoides vogae larvae (cestoda) under hypoxic and aerobic in vitro conditions. Molecules, 23.","DOI":"10.3390\/molecules23112999"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Yan, Y., Li, X., Zhang, C., Lv, L., Gao, B., and Li, M. (2021). Research progress on antibacterial activities and mechanisms of natural alkaloids: A review. Antibiotics, 10.","DOI":"10.3390\/antibiotics10030318"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.molcel.2012.04.027","article-title":"Antibiotic-induced bacterial cell death exhibits physiological and biochemical hallmarks of apoptosis","volume":"46","author":"Dwyer","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/jam.14632","article-title":"Antibacterial action of lactoferricin B like peptide against Escherichia coli: Reactive oxygen species-induced apoptosis-like death","volume":"129","author":"Lee","year":"2020","journal-title":"J. Appl. Microbiol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Erental, A., Sharon, I., and Engelberg-Kulka, H. (2012). Two programmed cell death systems in Escherichia coli: An apoptotic-like death is inhibited by the mazEF-mediated death pathway. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001281"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Vaou, N., Stavropoulou, E., Voidarou, C., Tsakris, Z., Rozos, G., Tsigalou, C., and Bezirtzoglou, E. (2022). Interactions between medical plant-derived bioactive compounds: Focus on antimicrobial combination effects. Antibiotics, 11.","DOI":"10.3390\/antibiotics11081014"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.semcancer.2020.09.014","article-title":"Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance","volume":"73","author":"Tuli","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1124\/dmd.107.017566","article-title":"Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract","volume":"36","author":"Wen","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1177\/0091270009347475","article-title":"Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C","volume":"50","author":"Hawke","year":"2010","journal-title":"J. Clin. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.etap.2014.05.005","article-title":"Hepatoprotective effect of silymarin on di (2-ethylhexyl) phthalate (DEHP) induced injury in liver FL83B cells","volume":"38","author":"Lo","year":"2014","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"593","DOI":"10.5414\/CPP41593","article-title":"Comparative bioavailability of silibinin in healthy male volunteers","volume":"41","author":"Kim","year":"2003","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.3748\/wjg.v17.i18.2288","article-title":"Silybin and the liver: From basic research to clinical practice","volume":"17","author":"Loguercio","year":"2011","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bbrc.2023.07.045","article-title":"Alleviation of acetaminophen-induced liver failure using silibinin nanoliposomes: An in vivo study","volume":"676","author":"Gheybi","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Durymanov, M., Permyakova, A., and Reineke, J. (2020). Pre-treatment with PLGA\/silibinin nanoparticles mitigates dacarbazine-induced hepatotoxicity. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00495"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/11\/1091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:33:04Z","timestamp":1760113984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/11\/1091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,15]]},"references-count":98,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["antibiotics13111091"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13111091","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,15]]}}}