Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives.

ABC superfamily Adriamycin BCRP P-glycoprotein expression profile immunomodulation silychristin silymarin

Journal

Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981

Informations de publication

Date de publication:
14 Aug 2019
Historique:
received: 27 06 2019
revised: 08 08 2019
accepted: 12 08 2019
entrez: 17 8 2019
pubmed: 17 8 2019
medline: 17 8 2019
Statut: epublish

Résumé

Silychristin A is the second most abundant compound of silymarin. Silymarin complex was previously described as an antioxidant with multidrug resistance modulation activity. Here, the results of a classical biochemical antioxidant assay (ORAC) were compared with a cellular assay evaluating the antioxidant capacity of pure silychristin A and its derivatives (anhydrosilychristin, isosilychristin and 2,3-dehydrosilychristin A). All the tested compounds acted as antioxidants within the cells, but 2,3-dehydro- and anhydro derivatives were almost twice as potent as the other tested compounds. Similar results were obtained in LPS-stimulated macrophages, where 2,3-dehydro- and anhydrosilychristin inhibited NO production nearly twice as efficiently as silychristin A. The inhibition of P-glycoprotein (P-gp) was determined in vitro, and the respective sensitization of doxorubicin-resistant ovarian carcinoma overproducing P-gp was detected. Despite the fact that the inhibition of P-gp was demonstrated in a concentration-dependent manner for each tested compound, the sensitization of the resistant cell line was observed predominantly for silychristin A and 2,3-dehydrosilychristin A. However, anhydrosilychristin and isosilychristin affected the expression of both the P-gp (

Identifiants

pubmed: 31416138
pii: antiox8080303
doi: 10.3390/antiox8080303
pmc: PMC6720199
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Ministerstvo Školství, Mládeže a Tělovýchovy
ID : INTER-COST LTC19007 and LTC19020
Organisme : Grantová agentura České Republiky
ID : 18-00150S
Organisme : Operational Program Prague-Competitiveness
ID : CZ.2.16/3.1.00/21537 and CZ.2.16/3.1.00/24503
Organisme : Czech National Program of Sustainability
ID : NPU I (LO) (MSMT-43760/2015)

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Auteurs

Jitka Viktorová (J)

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, CZ 166 28 Prague, Czech Republic. prokesoj@vscht.cz.

Simona Dobiasová (S)

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, CZ 166 28 Prague, Czech Republic.

Kateřina Řehořová (K)

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, CZ 166 28 Prague, Czech Republic.

David Biedermann (D)

Laboratory of Biotransformation, Institute of Microbiology, Czech Academy of Sciences, Vídeňská 1083, CZ 142 20 Prague, Czech Republic.

Kristýna Káňová (K)

Laboratory of Biotransformation, Institute of Microbiology, Czech Academy of Sciences, Vídeňská 1083, CZ 142 20 Prague, Czech Republic.

Karolína Šeborová (K)

Toxicogenomics Unit, National Institute of Public Health, Šrobárova 49, CZ 100 00 Prague, Czech Republic.
Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, alej Svobody 1655, CZ 323 00 Pilsen, Czech Republic.

Radka Václavíková (R)

Toxicogenomics Unit, National Institute of Public Health, Šrobárova 49, CZ 100 00 Prague, Czech Republic.
Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, alej Svobody 1655, CZ 323 00 Pilsen, Czech Republic.

Kateřina Valentová (K)

Laboratory of Biotransformation, Institute of Microbiology, Czech Academy of Sciences, Vídeňská 1083, CZ 142 20 Prague, Czech Republic.

Tomáš Ruml (T)

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, CZ 166 28 Prague, Czech Republic.

Vladimír Křen (V)

Laboratory of Biotransformation, Institute of Microbiology, Czech Academy of Sciences, Vídeňská 1083, CZ 142 20 Prague, Czech Republic.

Tomáš Macek (T)

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, CZ 166 28 Prague, Czech Republic.

Classifications MeSH