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Outline
To explore the effects of Zhimu extract on the absorption and pharmacokinetic process of puerarin, thus to elucidate the scientific connotation of the compatibility application of Gegen-Zhimu herb pair from the perspective of P-glycoprotein (P-gp) regulation, a rapid and sensitive quantification method for puerarin in biological samples was established based on HPLC-UV technology. Combined with the rat single-pass intestinal perfusion model and pharmacokinetic experiments, with the classic P-gp inhibitor verapamil as control, the effects of Zhimu extract on the absorption and metabolism process of puerarin were investigated. The established HPLC method for puerarin in intestine perfusate and plasma samples met the requirements for quantitative analysis of biological samples. The Ka and Papp values of puerarin in the duodenal segment were significantly higher than those in the jejunal and ileal segments (P < 0.000 1). Co-administration with Zhimu extract or verapamil significantly increased the Ka and Papp values of puerarin in the duodenal segment (P < 0.000 1). Co-administration with high-dose Zhimu extract or verapamil significantly increased the Cmax of puerarin in rats to (1.017 ± 0.25) µg·mL-1 and (1.827 ± 0.87) µg·mL-1 (P < 0.05), respectively, and AUC0-∞ also significantly increased (P < 0.05), reaching 1.37-fold and 2.25-fold that of the puerarin group, respectively. Puerarin is best absorbed in the duodenal segment; by inhibiting the efflux of P-gp, Zhimu extract can promote the absorption of puerarin in the duodenal segment, increase its plasma concentration, and effectively improve the oral bioavailability of puerarin, which suggests the mechanism underlying the compatibility of Gegen-Zhimu herb pair. This experiment was approved by the Animal Ethics Committee of Naval Medical University (approval No.: NMUARE-21077).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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