Pharmacokinetic investigation of principal active constituents in renal fibrotic rats after oral administration of crude and salt-processed eucommiae cortex extracts
10.16438/j.0513-4870.2022-1231
- VernacularTitle:杜仲盐炙前后主要活性成分在肾纤维化大鼠体内的药代动力学研究
- Author:
Meng-qing WANG
1
;
Hao CAI
1
;
Xin LIU
1
;
Jian-tao SONG
1
;
Gang CAO
2
;
Hui ZHU
1
;
Yu DUAN
1
;
Ke PEI
3
Author Information
1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China
2. School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China
3. School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong 030619, China
- Publication Type:Research Article
- Keywords:
Eucommiae Cortex;
salt-processing;
renal fibrosis;
pharmacokinetics;
UHPLC-QqQ-MS/MS
- From:
Acta Pharmaceutica Sinica
2023;58(6):1611-1618
- CountryChina
- Language:Chinese
-
Abstract:
A quantitative analysis method for six principal active constituents (acubin, geniposidic acid, chlorogenic acid, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside) of crude Eucommiae Cortex (EC) and its salt-processed product extracts was developed to investigate and compare their pharmacokinetic behaviors in adenine-induced renal fibrotic rats in vivo. UHPLC-QqQ-MS/MS technology was employed. Scan was conducted in negative ion mode and quantitative determination was carried out by MRM paired ion. The established method was fully validated by specificity, linearity, precision, accuracy, stability, recovery, and matrix effect, and the results of methodological investigation met the requirements of biological sample analysis. Then, a quick, sensitive, and accurate method was successfully established, which could simultaneously measure the contents of six active constituents of crude and salt-processed EC extracts in rat plasma. After a single administration to renal fibrotic rats of crude EC and its salt-processed product extracts, the plasma concentration of each constituent at different time points was measured, the pharmacokinetic parameters were calculated and the concentration time curves were structured. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that compared to the crude Eucommiae Cortex group, the tmax of aucubin, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside in the salt-processed Eucommiae Cortex group rat plasma were significantly lower than those in the crude group (P < 0.05, P < 0.01); the Cmax and AUC0-48 h of chlorogenic acid, the Cmax, AUC0-48 h and AUC0-∞ of pinoresinol di-O-glucopyranoside, and the Cmax of geniposide and pinoresinol 4-O-glucopyranoside were significantly higher than those in the crude group (P < 0.05, P < 0.01). Our investigation found that compared to crude Eucommiae Cortex, a variety of active ingredients could play a role of quick effect with higher peak blood concentration and bioavailability after oral administration of salt-processed Eucommiae Cortex, which were consistent with the traditional Chinese medicine theory of "salt-processing enhancing drug into kidney meridian", providing an experimental basis for the selection of quality control indexes and the in-depth study of processing mechanisms and metabolic rules in vivo of Eucommiae Cortex and its salt-processed product.
