In:
Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2019 ( 2019-02-12), p. 1-12
Abstract:
Bilirubin is considered to be one of the most potent endogenous antioxidants in humans. Its serum concentrations are predominantly affected by the activity of hepatic bilirubin UDP-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. This phenomenon might contribute to the hepatoprotective effects of silymarin.
Type of Medium:
Online Resource
ISSN:
1942-0900
,
1942-0994
DOI:
10.1155/2019/6026902
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2019
detail.hit.zdb_id:
2455981-7
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