Metabolism of 2,3-Dehydrosilybin A and 2,3-Dehydrosilybin B: A Study with Human Hepatocytes and Recombinant UDP-Glucuronosyltransferases and Sulfotransferases
Abstract
:1. Introduction
2. Materials and Methods
2.1. Tested Compounds
2.2. Incubation of 2,3-Dehydrosilybin A and B with Human Hepatocytes
2.3. Incubation of 2,3-Dehydrosilybin A and B with Human UGTs
2.4. Incubation of 2,3-Dehydrosilybin A and B with Human Sulfotransferases
2.5. UHPLC-MSE Analysis
3. Results and Discussion
3.1. Biotransformation of 2,3-Dehydrosilybin A and B in Human Hepatocytes
3.2. Glucuronidation of 2,3-Dehydrosilybin A and B by Individual Human UGTs
3.3. Sulfation of 2,3-Dehydrosilybin A and B by Individual Human Sulfotransferases
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Semiquantitative Percentage 2 | ||||||
---|---|---|---|---|---|---|
2,3-Dehydrosilybin A | 2,3-Dehydrosilybin B | |||||
Metabolic Reaction | Formula | m/z 1 | Cells | Medium | Cells | Medium |
Parent compound | C25H20O10 | 479.0974 | 85.1 | 70.5 | 83.1 | 75.8 |
Hydroxylation | C25H20O11 | 495.0921 | 0.4 | 0.0 | 0.4 | 0.0 |
Hydroxylation and methylation | C26H22O11 | 509.1084 | 0.9 | 0.7 | 1.0 | 1.1 |
Glucuronidation | C31H28O16 | 655.1287 | 9.2 | 24.7 | 13.0 | 20.2 |
Sulfation | C25H20O13S | 559.0513 | 2.0 | 2.8 | 2.2 | 2.9 |
Methylation | C26H22O10 | 493.1132 | 2.4 | 1.3 | 0.3 | 0.0 |
Semiquantitative Percentage 2 | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
UGT | ||||||||||||||
Compound/Metabolite | tR 1 (min) | 1A1 | 1A3 | 1A4 | 1A6 | 1A7 | 1A8 | 1A9 | 1A10 | 2B4 | 2B7 | 2B10 | 2B15 | 2B17 |
2,3-Dehydrosilybin A | 5.87 | 93.3 | 99.9 | 100.0 | 100.0 | 93.0 | 99.5 | 99.7 | 99.9 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
Glucuronide (1) | 4.80 | 1.1 | 0.1 | – | – | 0.2 | 0.3 | 0.1 | <0.1 | – | – | – | – | – |
Glucuronide (2) | 5.02 | 5.6 | – | – | – | 6.8 | 0.2 | 0.2 | <0.1 | – | – | – | – | – |
Glucuronide (3) | 5.43 | – | – | – | – | <0.1 | – | – | – | – | – | – | – | – |
2,3-Dehydrosilybin B | 5.90 | 99.1 | 99.9 | 100.0 | 100.0 | 99.5 | 99.6 | 92.9 | 99.8 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
Glucuronide (1) | 4.80 | 0.6 | <0.1 | – | – | 0.2 | 0.1 | 0.9 | <0.1 | – | – | – | – | – |
Glucuronide (2) | 5.02 | 0.2 | <0.1 | – | – | 0.3 | 0.3 | 6.2 | 0.1 | – | – | – | – | – |
Glucuronide (3) | 5.24 | 0.1 | – | – | – | – | – | – | 0.1 | – | – | – | – | – |
Semiquantitative Percentage 2 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
SULT | ||||||||||
Compound/Metabolite | tR 1 (min) | 1A1*1 | 1A1*2 | 1A2 | 1A3 | 1B1 | 1C2 | 1C4 | 1E1 | 2A1 |
2,3-Dehydrosilybin A | 5.89 | 99.8 | 99.7 | 99.2 | 97.8 | 98.6 | 99.8 | 98.7 | 99.0 | 100.0 |
Sulfate (1) | 5.25 | <0.1 | <0.1 | 0.1 | 2.2 | 1.3 | 0.2 | 0.8 | 0.1 | – |
Sulfate (2) | 5.50 | 0.2 | 0.2 | 0.7 | – | 0.1 | – | 0.5 | 0.9 | – |
2,3-Dehydrosilybin B | 5.92 | 99.6 | 99.6 | 99.6 | 98.0 | 99.2 | 99.7 | 98.1 | 98.5 | 100.0 |
Sulfate (1) | 5.26 | 0.1 | <0.1 | <0.1 | 2.0 | 0.2 | 0.3 | 1.9 | – | – |
Sulfate (2) | 5.45 | 0.3 | 0.4 | 0.4 | – | 0.6 | – | – | 1.5 | – |
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Vrba, J.; Papoušková, B.; Lněničková, K.; Kosina, P.; Křen, V.; Ulrichová, J. Metabolism of 2,3-Dehydrosilybin A and 2,3-Dehydrosilybin B: A Study with Human Hepatocytes and Recombinant UDP-Glucuronosyltransferases and Sulfotransferases. Antioxidants 2021, 10, 954. https://doi.org/10.3390/antiox10060954
Vrba J, Papoušková B, Lněničková K, Kosina P, Křen V, Ulrichová J. Metabolism of 2,3-Dehydrosilybin A and 2,3-Dehydrosilybin B: A Study with Human Hepatocytes and Recombinant UDP-Glucuronosyltransferases and Sulfotransferases. Antioxidants. 2021; 10(6):954. https://doi.org/10.3390/antiox10060954
Chicago/Turabian StyleVrba, Jiří, Barbora Papoušková, Kateřina Lněničková, Pavel Kosina, Vladimír Křen, and Jitka Ulrichová. 2021. "Metabolism of 2,3-Dehydrosilybin A and 2,3-Dehydrosilybin B: A Study with Human Hepatocytes and Recombinant UDP-Glucuronosyltransferases and Sulfotransferases" Antioxidants 10, no. 6: 954. https://doi.org/10.3390/antiox10060954
APA StyleVrba, J., Papoušková, B., Lněničková, K., Kosina, P., Křen, V., & Ulrichová, J. (2021). Metabolism of 2,3-Dehydrosilybin A and 2,3-Dehydrosilybin B: A Study with Human Hepatocytes and Recombinant UDP-Glucuronosyltransferases and Sulfotransferases. Antioxidants, 10(6), 954. https://doi.org/10.3390/antiox10060954