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1. This study aimed to investigate the pharmacokinetic interaction of the three ingredients in a traditional Chinese herbal formulation, Sini Decoction, and provide evidence for its compatibility mechanism. 2. First, the effect of liquiritin and 6-gingerol on the pharmacokinetic parameters of aconitine was investigated in rats by using a sensitive and reliable LC-MS/MS method. Then the Caco-2 cell monolayer model and Rhodamine-123 uptake assay were used to investigate the effect of liquiritin and 6-gingerol on the absorption of aconitine and the activity of P-gp. 3. The C max of aconitine increased significantly (p < 0.05) from 10.34 ± 1.99 to 17.68 ± 2.65 ng/mL with the pretreatment of liquiritin (20 mg/kg), and to 17.43 ± 0.96 ng/mL with 6-gingerol (20 mg/kg). When aconitine was co-administered with liquiritin and 6-gingerol, the C max and AUC (0 of aconitine increased approximately twofold, and while t -t only increased 1.2-fold. The Caco-2 cell monolayer model and Rhodamine-123 uptake assay indicated that both liquiritin and 6-gingerol could increase the absorption of aconitine by inhibiting the activity of P-gp. 4. These results indicated that both liquiritin and 6-gingerol could promote the absorption of aconitine and increase its drug concentration in blood by inhibiting the activity of P-gp, and it could also provide evidence for compatibility mechanism of the traditional Chinese herbal formula, Sini Decoction.) of aconitine increased approximately twofold, and while t 1/2 only increased 1.2-fold. The Caco-2 cell monolayer model and Rhodamine-123 uptake assay indicated that both liquiritin and 6-gingerol could increase the absorption of aconitine by inhibiting the activity of P-gp. 4. These results indicated that both liquiritin and 6-gingerol could promote the absorption of aconitine and increase its drug concentration in blood by inhibiting the activity of P-gp, and it could also provide evidence for compatibility mechanism of the traditional Chinese herbal formula, Sini Decoction.

Sini decoction (SND) is an important traditional Chinese multiherbal formula, which is widely used to treat cardiovascular disease. Acontium carmichaeli (AC) is a leading herb in SND, whose main components are monoester-diterpenoid alkaloids (MDAs). The aim of this study is to compare the pharmacokinetics of three MDAs in rat plasma after oral administration of AC extract and its compatibility with other herbal medicines in SND. A sensitive, accurate and specific LC-MS/MS method was developed to determine the contents of three MDAs in rat plasma. Male Sprague-Dawley rats were randomly assigned to four groups: AC, AC + ZO, AC + GU and SND groups. There were significant differences in the pharmacokinetic parameters (Cmax, Tmax, t1/2, AUC(0-24), MRT and CL). Compared with the AC group, Cmax, AUC(0-24) and CL of three MDAs increased and t1/2 decreased in AC + ZO, AC + GU and SND groups. Little changed in the AC + GU group in comparison with AC + ZO group, which indicated that other ingredients in ZO may promote the absorption rate and accelerate excretion rate of MDAs. The results could be helpful for revealing the compatibility mechanism of Chinese multiherbal medicine and providing clinical medication guidance on AC and its compatibility with other herbal medicines in SND., (Copyright © 2014 John Wiley & Sons, Ltd.)