Influence of Jiegeng on Pharmacokinetic Properties of Flavonoids and Saponins in Gancao
Abstract
:1. Introduction
2. Results and Discussion
2.1. Oral Pharmacokinetics Study
2.2. Transcellular Transport of LQ, LG and GLY across Caco-2 Cell Monolayer
2.3. Hydrolysis of LQ, LG and GLY in Fecal Lysates
3. Materials and Methods
3.1. Reagents and Materials
3.2. Preparation of Sample Extracts
3.3. Animals
3.4. Pharmacokinetic Study
3.5. Cell Culture
3.6. Transport of LQ, LG and GLY across Caco-2 Cell Monolayer
3.7. Fecal Lysates Preparation
3.8. Metabolism of LQ, LG and GLY in Fecal Lysates
3.9. Quantification of Flavonoids and Saponins in Biological Matrices
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Parameter | LQ | ILQ | LG | |||
GC | JG–GC | GC | JG–GC | GC | JG–GC | |
Cmax (ng/mL) | 2.48 ± 72.6 | 294 ± 52.4 | 45.9 ± 14.5 | 35.6 ± 7.08 | 47.9 ± 9.24 | 37 ± 9.79 |
t1/2 (h) | 2.02 ± 0.90 | 2.54 ± 0.81 | 4.78 ± 0.84 | 2.93 ± 0.89 | 2.80 ± 0.19 | 2.54 ± 0.81 |
Tmax (h) | 0.14 ± 0.043 | 0.13 ± 0.046 | 0.25 ± 0.09 | 0.33 ± 0 | 0.78 ± 0.05 | 1.29 ± 0.05 |
AUC(0–t) (ng/mL·h) | 301.9 ± 58.1 | 1104.5 ± 270 * | 75.3 ± 17.6 | 136 ± 36.5 | 533.3 ± 191.8 | 304.4 ± 59.1 ** |
AUC(0–∞) (ng/mL·h) | 303 ± 58.4 | 1106 ± 269 * | 76.6 ± 17.2 | 137 ± 36.5 | 545 ± 213 | 262 ± 55.6 ** |
Parameter | ILG | GLY | GA | |||
GC | JG–GC | GC | JG–GC | GC | JG–GC | |
Cmax (ng/mL) | 45.2 ± 13.3 | 17.3 ± 5.09 * | 4102 ± 1307 | 5190 ± 1228 | 3109 ± 1007 | 7848 ± 1862 * |
t1/2 (h) | 3.37 ± 0.33 | 4.41 ± 1.04 | 3.03 ± 0.48 | 3.43 ± 0.87 | 4.22 ± 0.87 | 6.00 ± 1.78 |
Tmax (h) | 1.56 ± 0.25 | 1.78 ± 0.096 | 0.39 ± 0.11 | 4.83 ± 0.89 * | 11.3 ± 1.63 | 11.3 ± 1.63 |
AUC(0–t) (ng/mL·h) | 201.8 ± 54.4 | 120.4 ± 31.5 * | 13,530.7 ± 4038 | 41,241.1 ± 10,290 * | 40,353.5 ± 9018.2 | 117,529.5 ± 20,640.3 * |
AUC(0–∞) (ng/mL·h) | 205 ± 52.9 | 129 ± 21.5 | 13,532 ± 4037 | 41,248 ± 10,284 * | 40,418 ± 8993 | 118,998 ± 21,515 * |
Time (min) | Papp-LQ (1 × 10−6 cm/s) | Papp-LG (1 × 10−6 cm/s) | Papp-GLY (1 × 10−6 cm/s) | ||||||
---|---|---|---|---|---|---|---|---|---|
LQ | GC | JG–GC | LG | GC | JG–GC | GLY | GC | JG–GC | |
30 | 0.18 ± 0.01 | 2.03 ± 0.51 ** | 2.95 ± 0.47 ## | 9.80 ± 0.78 | 9.48 ± 1.35 | 8.98 ± 0.70 | 1.91 ± 0.23 | 1.94 ± 0.20 | 2.08 ± 0.21 |
60 | 0.37 ± 0.07 | 3.63 ± 0.47 ** | 3.71 ± 0.84 ## | 16.70 ± 3.30 | 15.30 ± 5.32 | 13.50 ± 0.19 | 2.90 ± 0.07 | 3.10 ± 0.20 | 3.03 ± 0.41 |
90 | 0.46 ± 0.13 | 4.90 ± 0.85 ** | 4.63 ± 0.23 ## | 26.10 ± 0.23 | 28.30 ± 2.12 | 26.30 ± 2.15 | 4.57 ± 0.29 | 4.19 ± 0.29 | 4.24 ± 0.26 |
120 | 0.88 ± 0.10 | 5.96 ± 0.38 ** | 5.65 ± 0.40 ## | 46.00 ± 3.07 | 46.70 ± 1.50 | 47.30 ± 3.15 | 4.91 ± 0.05 | 4.91 ± 0.18 | 5.08 ± 0.32 |
Analyte | LQ | ILQ | LG | ILG | GLY |
---|---|---|---|---|---|
(μg/mL) | (μg/mL) | (μg/mL) | (μg/mL) | (μg/mL) | |
JG–GC(3 g/mL) | 7100 | 600 | 2000 | 70 | 26,000 |
GC(2 g/mL) | 7500 | 560 | 2200 | 70 | 26,500 |
Group | LQ (ng/mL) | LG (ng/mL) | GLY (ng/mL) |
---|---|---|---|
JG–GC (1.5 mg/mL) | 3550 | 1000 | 13,000 |
GC (1 mg/mL) | 3750 | 1500 | 13,250 |
LQ | 3500 | / | / |
LG | / | 900 | / |
GLY | / | / | 13,200 |
LQ+JG | 3500 | / | / |
LG+JG | / | 900 | / |
GLY+JG | / | / | 13,200 |
Analyte | Rat Plasma | HBSS Buffer | Fecal Lysates | |||
---|---|---|---|---|---|---|
Linear Range | LLOQ | Linear Range | LLOQ | Linear Range | LLOQ | |
(ng/mL) | (ng/mL) | (ng/mL) | (ng/mL) | (ng/mL) | (ng/mL) | |
LG | 0.43–330 | 0.43 | 0.54–1100 | 0.54 | 2.15–2200 | 2.15 |
ILG | 0.41–315 | 0.41 | ||||
LQ | 0.47–360 | 0.47 | 1.47–3000 | 1.47 | 1.47–1500 | 1.47 |
ILQ | 0.40–306 | 0.4 | ||||
GLY | 10.26–7875 | 10.26 | 3.96–8100 | 3.96 | 5.27–5400 | 5.27 |
GA | 14.64–11,250 | 14.64 | 2.93–3000 | 2.93 |
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Mao, Y.; Peng, L.; Kang, A.; Xie, T.; Xu, J.; Shen, C.; Ji, J.; Di, L.; Wu, H.; Shan, J. Influence of Jiegeng on Pharmacokinetic Properties of Flavonoids and Saponins in Gancao. Molecules 2017, 22, 1587. https://doi.org/10.3390/molecules22101587
Mao Y, Peng L, Kang A, Xie T, Xu J, Shen C, Ji J, Di L, Wu H, Shan J. Influence of Jiegeng on Pharmacokinetic Properties of Flavonoids and Saponins in Gancao. Molecules. 2017; 22(10):1587. https://doi.org/10.3390/molecules22101587
Chicago/Turabian StyleMao, Yancao, Linxiu Peng, An Kang, Tong Xie, Jianya Xu, Cunsi Shen, Jianjian Ji, Liuqing Di, Hao Wu, and Jinjun Shan. 2017. "Influence of Jiegeng on Pharmacokinetic Properties of Flavonoids and Saponins in Gancao" Molecules 22, no. 10: 1587. https://doi.org/10.3390/molecules22101587