Effect of Water Extract of Mangosteen Pericarp on Donepezil Pharmacokinetics in Mice
Abstract
:1. Introduction
2. Results
2.1. Effect of WMP and Donepezil Hydrochloride (DNP) Combination on Cell Viability
2.2. Safety of WMP
2.3. Effect of WMP on the Pharmacokinetics of Donepezil
2.4. Effect of WMP on Tissue Distribution of Donepezil
2.5. Effect of WMP on Plasma Protein Binding of Donepezil in Mice
2.6. Effect of WMP on Donepezil Metabolism In Vitro S9 Fractions of Liver and Small Intestine
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Preparation and Analysis of WMP
4.3. Effect of WMP and DNP Combination on Cell Viability of SH-SY5Y Neuroblastoma Cells Treated with Aβ(25–35)
4.4. Animals
4.5. Toxicity Test of WMP
4.6. Effect of WMP on the Pharmacokinetics of Donepezil
4.7. Effect of WMP on Tissue Distribution of Donepezil
4.8. Effect of WMP on Plasma Protein Binding of Donepezil
4.9. Effect of WMP on Donepezil Metabolism in In Vitro S9 Fractions of Various Tissues
4.10. LC-MS/MS Analysis of Donepezil in Biological Samples
4.11. LC-MS/MS Analysis of the Tentative Metabolites of Donepezil
4.12. Analysis of Pharmacokinetic Parameters
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Parameters | DNP (n = 10 from 30 Mice) | DNPWMP (n = 10 from 28 Mice ) |
---|---|---|
Body weight (g) | 28.30 ± 0.63 | 27.84 ± 0.54 |
AUC360 min (μg min/mL) | 16.21 ± 4.42 | 12.22 ± 2.43 |
AUC0-∞ (μg min/mL) | 16.73 ± 4.16 | 12.60 ± 2.49 |
Terminal half-life (min) | 77.32 ± 32.33 | 65.11 ± 10.83 |
Cmax (μg/mL) | 0.24 ± 0.12 | 0.16 ± 0.45 |
Tmax (min)a | 15 (15−15) | 15 (15−30) |
Vc/F (mL/kg) | 23,672.72 ± 7403.86 | 20,631.21 ± 1272.14 |
Vp/F (mL/kg) | 4160.44 ± 592.25 | 3886.46 ± 800.54 |
ka (1/min) | 0.071 ± 0.031 | 0.056 ± 0.028 |
k12 (1/min) | 0.014 ± 0.010 | 0.012 ± 0.0042 |
k21 (1/min) | 0.0087 ± 0.0058 | 0.010 ± 0.0062 |
ke (1/min) | 0.027 ± 0.013 | 0.023 ± 0.0043 |
Ae0–24 h (% of dose) | 1.65 ± 0.35 | 0.73 ± 0.67 |
GI24 h (% of dose) | 0.036 ± 0.02 | 0.08 ± 0.064 |
Tissue | 1 h | 4 h | ||
---|---|---|---|---|
DNP (n = 5) | DNPWMP (n = 5) | DNP (n = 5) | DNPWMP (n = 5) | |
Plasma | 0.10 ± 0.05 | 0.10 ± 0.02 | 0.02 ± 0.01 * | 0.01 ± 0.01 * |
Brain | 2.17 ± 1.21 | 1.98 ± 0.53 | 0.22 ± 0.08 * | 0.36 ± 0.081 *,+ |
(21.42 ± 6.07) | (20.44 ± 5.72) | (20.41 ± 5.72) | (31.73 ± 12.12) + | |
Kidney | 10.27 ± 6.55 | 7.91 ± 1.74 | 0.96 ± 0.17 * | 0.90 ± 0.28 * |
(115 ± 64.79) | (82.37 ± 23.81) | (82.38 ± 23.79) | (78.27 ± 33.31) | |
Liver | 15.07 ± 2.23 | 18.5 ± 2.34+ | 2.79 ± 0.70 * | 3.53 ± 1.87 * |
(179 ± 85.28) | (191 ± 69.39) | (197 ± 69.42) | (285 ± 96.81) | |
Stomach | 23.57 ± 5.79 | 35.48 ± 13.63 | 3.35 ± 1.53 * | 4.75 ± 2.38 * |
(309 ± 196) | (379 ± 185) | (379 ± 185) | (426 ± 264) | |
Small intestine | 15.82 ± 7.93 | 26.08 ± 9.60 | 3.33 ± 1.54 * | 2.29 ± 0.97 * |
(177 ± 99.16) | (263 ± 84.92) | (263 ± 84.88) | (189 ± 63.79) | |
Large intestine | 15.33 ± 5.50 | 22.41 ± 13.92 | 2.39 ± 0.62 * | 1.58 ± 0.40 *,+ |
(183 ± 100) | (218 ± 119) | (218 ± 119) | (147 ± 73.40) |
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Bae, M.; Han, S.Y.; Kim, E.-S.; You, B.H.; Kim, Y.-M.; Cho, J.; Chin, Y.-W.; Choi, Y.H. Effect of Water Extract of Mangosteen Pericarp on Donepezil Pharmacokinetics in Mice. Molecules 2021, 26, 5246. https://doi.org/10.3390/molecules26175246
Bae M, Han SY, Kim E-S, You BH, Kim Y-M, Cho J, Chin Y-W, Choi YH. Effect of Water Extract of Mangosteen Pericarp on Donepezil Pharmacokinetics in Mice. Molecules. 2021; 26(17):5246. https://doi.org/10.3390/molecules26175246
Chicago/Turabian StyleBae, Mingoo, Seung Yon Han, Eun-Sun Kim, Byung Hoon You, Young-Mi Kim, Jungsook Cho, Young-Won Chin, and Young Hee Choi. 2021. "Effect of Water Extract of Mangosteen Pericarp on Donepezil Pharmacokinetics in Mice" Molecules 26, no. 17: 5246. https://doi.org/10.3390/molecules26175246