Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5′-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes
Abstract
:1. Introduction
2. Results and Discussion
3. Material and Methods
3.1. Reagents
3.2. Microsomal Incubation
3.2.1. Inhibitory Effects of Selaginellins on P450 Activity
3.2.2. Inhibitory Effects of Selaginellins on UGT Activity
3.3. Data Analysis
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Compound | IC50 (μM) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P450 Isoforms | UGT Isoforms | |||||||||||||||
1A2 | 2A6 | 2B6 | 2C8 | 2C9 | 2C19 | 2D6 | 2E1 | 2J2 | 3A | 1A1 | 1A3 | 1A4 | 1A6 | 1A9 | 2B7 | |
Selaginellin | 36.4 | >50 | 10.7 | 0.5 | 1.2 | 10.0 | 5.8 | 38.5 | 0.8 | 11.7 | 1.0 | 4.7 | 6.6 | 25.3 | 8.7 | 15.6 |
Selaginellin M | >50 | >50 | 11.3 | 0.9 | 3.9 | 16.1 | 6.8 | >50 | 2.7 | >50 | 1.3 | 3.5 | 3.9 | 36.5 | 6.5 | 10.4 |
Enzyme | Substrate | Concentration (μM) | Metabolite | Transition (m/z) | Collision Energy (eV) | Polarity * |
---|---|---|---|---|---|---|
CYP1A2 | Phenacetin | 100 | Acetaminophen | 152 > 110 | 25 | ESI+ |
CYP2A6 | Coumarin | 5.0 | Hydroxycoumarin | 163 > 107 | 17 | ESI+ |
CYP2B6 | Bupropion | 50 | Hydroxybupropion | 256 > 238 | 20 | ESI+ |
CYP2C8 | Amodiaquine | 1.0 | N-Desethylamodiaquine | 328 > 283 | 17 | ESI+ |
CYP2C9 | Tolbutamide | 100 | Hydroxytolbutamide | 287 > 89 | 42 | ESI+ |
CYP2C19 | Omeprazole | 20 | Hydroxyomeprazole | 362 > 214 | 10 | ESI+ |
CYP2D6 | Dextromethorphan | 5.0 | Dextrorphan | 258 > 157 | 35 | ESI+ |
CYP2E1 | Chlorzoxazone | 50 | Hydroxychlorzoxazone | 184 > 120 | 15 | ESI− |
CYP2J2 | Astemizole | 1.0 | O-Desmethyl astemizole | 445 > 204 | 35 | ESI+ |
CYP3A | Midazolam | 5.0 | Hydroxymidazolam | 342 > 203 | 25 | ESI+ |
UGT1A1 | SN-38 | 0.5 | SN-38-glucuronide | 569 > 393 | 30 | ESI+ |
UGT1A3 | Chenodeoxycholic acid | 2.0 | Chenodeoxycholic acid glucuronide | 567 > 391 | 35 | ESI− |
UGT1A4 | Trifluoperazine | 0.5 | Trifluoperazine glucuronide | 584 > 408 | 25 | ESI+ |
UGT1A6 | N-Acetylserotonin | 1.0 | N-Acetylserotonin glucuronide | 395 > 219 | 15 | ESI+ |
UGT1A9 | Mycophenolic acid | 0.2 | Mycophenolic acid glucuronide | 495 > 319 | 20 | ESI− |
UGT2B7 | Naloxone | 1.0 | Naloxone glucuronide | 504 > 310 | 30 | ESI+ |
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Heo, J.-K.; Nguyen, P.-H.; Kim, W.C.; Phuc, N.M.; Liu, K.-H. Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5′-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes. Molecules 2017, 22, 1590. https://doi.org/10.3390/molecules22101590
Heo J-K, Nguyen P-H, Kim WC, Phuc NM, Liu K-H. Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5′-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes. Molecules. 2017; 22(10):1590. https://doi.org/10.3390/molecules22101590
Chicago/Turabian StyleHeo, Jae-Kyung, Phi-Hung Nguyen, Won Cheol Kim, Nguyen Minh Phuc, and Kwang-Hyeon Liu. 2017. "Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5′-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes" Molecules 22, no. 10: 1590. https://doi.org/10.3390/molecules22101590