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

0510067 - MBÚ 2020 RIV CH eng J - Článek v odborném periodiku
Viktorová, J. - Dobiášová, S. - Řehořová, K. - Biedermann, David - Káňová, Kristýna - Šeborová, K. - Václavíková, R. - Valentová, Kateřina - Ruml, T. - Křen, Vladimír - Macek, T.
Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives.
Antioxidants. Roč. 8, č. 8 (2019), č. článku 303. E-ISSN 2076-3921
Grant CEP: GA ČR(CZ) GA18-00150S
Institucionální podpora: RVO:61388971
Klíčová slova: Adriamycin * P-glycoprotein * silymarin
Obor OECD: Medicinal chemistry
Impakt faktor: 5.014, rok: 2019
Způsob publikování: Open access
https://www.mdpi.com/2076-3921/8/8/303

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.
Trvalý link: http://hdl.handle.net/11104/0300624