Flavonoids are naturally occurring compounds found in fruits, vegetables, and other plant-based foods, and they are known for their health benefits, such as UV protection, antioxidant, anti-inflammatory, and antiproliferative properties. This study investigates whether flavonoids, such as quercetin and 2,3-dehydrosilybin, can act as photoactivatable carbon monoxide (CO)-releasing molecules under physiological conditions. CO has been recently recognized as an important signaling molecule. Here, we show that upon direct irradiation, CO was released from both flavonoids in PBS with chemical yields of up to 0.23 equiv, which increased to almost unity by sensitized photooxygenation involving singlet oxygen. Photoreleased CO reduced cellular toxicity caused by high flavonol concentrations, partially restored mitochondrial respiration, reduced superoxide production induced by rotenone and high flavonol levels, and influenced the G0/G1 and G2/M phases of the cell cycle, showing antiproliferative effects. The findings highlight the potential of quercetin and 2,3-dehydrosilybin as CO-photoreleasing molecules with chemopreventive and therapeutic implications in human pathology and suggest their possible roles in plant biology.

• Klíčová slova
• 2,3-dehydrosilybin, carbon monoxide, cell cycle, mitochondrial respiration, oxidative stress, photoCORM, photoinduced release, quercetin,
• MeSH
• buněčný cyklus účinky léků   MeSH
• flavonoidy * chemie   farmakologie   MeSH
• lidé MeSH
• oxid uhelnatý * metabolismus   chemie   MeSH
• proliferace buněk účinky léků   MeSH
• quercetin farmakologie   chemie   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• rostliny chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• flavonoidy * MeSH
• oxid uhelnatý * MeSH
• quercetin MeSH
• rostlinné extrakty MeSH

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 ± 0.03vs.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.

• MeSH
• bilirubin metabolismus   MeSH
• buňky Hep G2 MeSH
• flavonoidy chemie   izolace a purifikace   farmakologie   MeSH
• glukuronosyltransferasa genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• intracelulární prostor metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši inbrední C57BL MeSH
• peroxidace lipidů účinky léků   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• silibinin aplikace a dávkování   farmakologie   MeSH
• silymarin izolace a purifikace   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bilirubin MeSH
• flavonoidy MeSH
• glukuronosyltransferasa MeSH
• hemoxygenasa-1 MeSH
• HMOX1 protein, human MeSH Prohlížeč
• messenger RNA MeSH
• silibinin MeSH
• silymarin MeSH
• UGT1A1 enzyme MeSH Prohlížeč