Studying the effects of Saposhnikoviae Radix on the pharmacokinetic profiles of 10 bioactive compounds originating from Astragali Radix in rat plasma by UHPLC-QTRAP-MS/MS

Abstract

Ethnopharmacological relevance

Astragali Radix-Saposhnikoviae Radix (AR-SR) is a well-known and effective herb pair. Although the compatibility of these two herbs has been widely applied in many traditional Chinese medicine formulas, its potential mechanism still needs to be investigated.

Aim of study

To evaluate the pharmacokinetic profiles of 10 bioactive compounds derived from AR when administrated alone and in combination with SR to rats, aiming to further reveal the impact of SR on AR.

Materials and methods

Two groups of male Sprague-Dawley rats received oral administration of AR and AR-SR freeze-dried powder solutions, respectively. UHPLC-QTRAP-MS/MS technology was utilized to perform the pharmacokinetic studies of 10 compounds derived from AR in rat plasma samples.

Results

A reliable UHPLC-QTRAP-MS/MS method was established to simultaneously determine the rat plasma concentrations of eight isoflavonoids, referring to calycosin (CAL), calycosin-7-O-β-D-glucoside (CAL-G), formononetin (FOR), formononetin-7-O-β-D-glucoside (FOR-G), astrapterocarpan (APC), astrapterocarpan-3-O-β-D-glucoside (APC-G), astraisoflavan-7-O-β-D-glucoside (AIF-G) and formononetin-7-O-β-D-glucuronide (FOR-GN), and two saponins, including astragaloside IV (AS IV) and cycloastragenol (CAG), originating from AR. Following the oral administration of AR, seven isoflavonoids were quickly absorbed but exhibited low plasma concentrations under 17.88 ng/mL except FOR-GN. The latter maintained higher plasma concentration level more than 15 ng/mL for at least 10 h. Besides, for the first time, AS IV was observed with an obvious double-peak phenomenon after administering AR extract, whereas the concentration of CAG was lower than LLOQ before 6 h. When AR and SR were administrated together, the double-peak phenomena of CAL, FOR, APC, AIF-G and FOR-GN were enhanced and there was a significant increase in their values of area under the concentration-time curve (AUC) and mean residence time (MRT) (P < 0.05) while the pharmacokinetic profiles of CAL-G, FOR-G, APC-G, AS IV and CAG stayed almost unchanged (P > 0.05). Moreover, the elimination half-time (t_1/2) values of CAL, FOR and APC were significantly elevated, and the clearance rate/bioavailability (CL_z/F) for CAL and FOR was reduced (P < 0.05).

Conclusions

SR has the potential to modulate the ADME process of five out of the eight isoflavonoids (CAL, FOR, APC, AIF-G and FOR-GN, except CAL-G, FOR-G and APC-G) originating from AR. This interaction is especially likely to affect the hepatic and intestinal drug disposition of these isoflavonoids, thereby extending the duration of their pharmacological effects, which may subsequently impact the therapeutic efficacy of AR.