Isolated Silymarin Flavonoids Increase Systemic and Hepatic Bilirubin Concentrations and Lower Lipoperoxidation in Mice

0503924 - MBÚ 2020 RIV GB eng J - Článek v odborném periodiku
Šuk, J. - Jašprová, J. - Biedermann, David - Petrásková, Lucie - Valentová, Kateřina - Křen, Vladimír - Muchová, L. - Vítek, L.
Isolated Silymarin Flavonoids Increase Systemic and Hepatic Bilirubin Concentrations and Lower Lipoperoxidation in Mice.
Oxidative Medicine and Cellular Longevity. Roč. 2019, č. 1 (2019), č. článku 6026902. ISSN 1942-0900. E-ISSN 1942-0994
Grant CEP: GA MZd(CZ) NV16-27317A
Institucionální podpora: RVO:61388971
Klíčová slova: serum bilirubin * intravenous silibinin * gilbert-syndrome
Obor OECD: Medicinal chemistry
Impakt faktor: 5.076, rok: 2019
Způsob publikování: Open access
https://www.hindawi.com/journals/omcl/2019/6026902/

Bilirubin is one of the most potent endogenous antioxidants in humans. Its serum concentrations are predominantly affected by the activity of hepatic bilirubin LIDP-glucuronosyl transferase (UGT1A1). Our objective was to analyze the potential bilirubin-modulating effects of natural polyphenols from milk thistle (Silybum marianum), a hepatoprotective herb. Human hepatoblastoma HepG2 cells were exposed to major polyphenolic compounds isolated from milk thistle. Based on in vitro studies, 2,3-dehydrosilybins A and B were selected as the most efficient compounds and applied either intraperitoneally or orally for seven days to C57BL/6 mice. After, UGT1A1 mRNA expression, serum, intrahepatic bilirubin concentrations, and lipoperoxidation in the liver tissue were analyzed. All natural polyphenols used increased intracellular concentration of bilirubin in HepG2 cells to a similar extent as atazanavir, a known bilirubinemia-enhancing agent. Intraperitoneal application of 2,3-dehydrosilybins A and B (the most efficient flavonoids from in vitro studies) to mice (50 mg/kg) led to a significant downregulation of UGT1A1 mRNA expression (46 +/- 3% of controls, p < 0.005) in the liver and also to a significant increase of the intracellular bilirubin concentration (0.98 +/- 0.03 vs. 1.21 +/- 0.02 nmol/mg, p < 0.05). Simultaneously, a significant decrease of lipoperoxidation (61 +/- 2% of controls, p < 0.005) was detected in the liver tissue of treated animals, and similar results were also observed after oral treatment. Importantly, both application routes also led to a significant elevation of serum bilirubin concentrations (125 +/- 3% and 160 +/- 22% of the controls after intraperitoneal and oral administration, respectively, p < 0.005 in both cases). In conclusion, polyphenolic compounds contained in silymarin, in particular 2,3-dehydrosilybins A and B, affect hepatic and serum bilirubin concentrations, as well as lipoperoxidation in the liver.
Trvalý link: http://hdl.handle.net/11104/0295692