Pharmacokinetic interaction of aconitine, liquiritin and 6-gingerol in a traditional Chinese herbal formula, Sini Decoction.

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 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 and AUC of aconitine increased approximately twofold, and while 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.