title: Pharmacokinetic interaction of aconitine, liquiritin and 6-gingerol in a traditional Chinese herbal formula, Sini Decoction.
abstract: 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 Cmaxof 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 Cmaxand AUC(0-t)of aconitine increased approximately twofold, and while t1/2only 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.
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Sen
authors.initials: S
authors.lastname: Sun
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Ge
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacy , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai , China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000157:Aconitine / Q000493:pharmacokinetics*; D000818:Animals; D018938:Caco-2 Cells; D002396:Catechols / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D005233:Fatty Alcohols / Q000493:pharmacokinetics*; D044950:Flavanones / Q000493:pharmacokinetics*; D005960:Glucosides / Q000493:pharmacokinetics*; D006801:Humans; D008516:Medicine, Chinese Traditional; D051381:Rats
chemical_list: D002396:Catechols; D004365:Drugs, Chinese Herbal; D005233:Fatty Alcohols; D044950:Flavanones; D005960:Glucosides; C478756:sini tang; C007845:gingerol; C512196:liquiritin; D000157:Aconitine
keywords: 6-gingerol; Aconitine; LC–MS/MS; Sini Decoction; compatibility mechanism; liquiritin; pharmacokinetic interaction