Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives
AbstractSilychristin 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. View Full-Text
Share & Cite This Article
Viktorová, J.; Dobiasová, S.; Řehořová, K.; Biedermann, D.; Káňová, K.; Šeborová, K.; Václavíková, R.; Valentová, K.; Ruml, T.; Křen, V.; Macek, T. Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives. Antioxidants 2019, 8, 303.
Viktorová J, Dobiasová S, Řehořová K, Biedermann D, Káňová K, Šeborová K, Václavíková R, Valentová K, Ruml T, Křen V, Macek T. Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives. Antioxidants. 2019; 8(8):303.Chicago/Turabian Style
Viktorová, Jitka; Dobiasová, Simona; Řehořová, Kateřina; Biedermann, David; Káňová, Kristýna; Šeborová, Karolína; Václavíková, Radka; Valentová, Kateřina; Ruml, Tomáš; Křen, Vladimír; Macek, Tomáš. 2019. "Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives." Antioxidants 8, no. 8: 303.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.