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Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives
J. Viktorová, S. Dobiasová, K. Řehořová, D. Biedermann, K. Káňová, K. Šeborová, R. Václavíková, K. Valentová, T. Ruml, V. Křen, T. Macek,
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
INTER-COST LTC19007 and LTC19020
Ministerstvo Školství, Mládeže a Tělovýchovy
18-00150S
Grantová agentura České Republiky
CZ.2.16/3.1.00/21537 and CZ.2.16/3.1.00/24503
Operational Program Prague-Competitiveness
NPU I (LO) (MSMT-43760/2015)
Czech National Program of Sustainability
PubMed Central od 2012
Europe PubMed Central od 2012
ProQuest Central od 2012-03-01
Open Access Digital Library od 2012-01-01
Open Access Digital Library od 2012-01-01
ROAD: Directory of Open Access Scholarly Resources od 2012
Odkazy
PubMed
31416138
DOI
10.3390/antiox8080303
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
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 (ABCB1) and ABCG2 genes. This is the first report showing that silychristin A and its 2,3-dehydro-derivative modulate multidrug resistance by the direct inhibition of P-gp, in contrast to anhydrosilychristin and isosilychristin modulating multidrug resistance by downregulating the expression of the dominant transmembrane efflux pumps.
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- $a Viktorová, Jitka $u Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, CZ 166 28 Prague, Czech Republic. prokesoj@vscht.cz.
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- $a 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 (ABCB1) and ABCG2 genes. This is the first report showing that silychristin A and its 2,3-dehydro-derivative modulate multidrug resistance by the direct inhibition of P-gp, in contrast to anhydrosilychristin and isosilychristin modulating multidrug resistance by downregulating the expression of the dominant transmembrane efflux pumps.
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- $a Dobiasová, Simona $u Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, CZ 166 28 Prague, Czech Republic.
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- $a Václavíková, Radka $u 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.
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