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 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.

Enhanced oral bioavailability and anti‐hyperuricemic activity of liquiritin via a self‐nanoemulsifying drug delivery system

“…Based on the above results, it was predicted that the optimized formulation could increase the solubility and absorption of LQ. The available literature posits that liquiritin can inhibit P‐glycoprotein (P‐gp), which may improve its uptake and absorption in the intestine 20 . Non‐ionic surfactants like Tween 80 have been found to inhibit P‐gp, which increases the intestinal absorption of lipophilic drugs 21 .…”

Research Progress on the Mechanism of Reducing Toxicity and Increasing the Efficacy of Sini Decoction Compatibility

“…57) Meanwhile, a previous pharmacokinetic research has shown that a major component of 6-gingerol in Aconitum carmichaelii and liquiritin promoted the absorption of aconitine, and enhanced its drug concentration in blood. 18) What's more, compared with Aconitum carmichaelii, the bioavailability of diester diterpenoid alkaloids decreased, and the content of the diester diterpenoid alkaloids was reduced in SND. 58,59) CYP isozymes can be induced or inhibited by a variety of drugs, which may lead to drug interactions and increase the incidence of clinical adverse reactions.…”

“…Through compatibility, SND can produce better synergism and detoxification. 18) In addition, as Aconitum carmichaelii is the principal medicine in SND, it also has certain toxic and other side effects. Hence, there are many records of different processed products of Aconitum carmichaelii in SND such as raw Aconitum carmichaelii in Treatise on febrile diseases and Danfupian in Chinese Pharmacopoeia (2020).…”

Metabolite Profiling Analysis of the Tongmai Sini Decoction in Rats after Oral Administration through UHPLC-Q-Exactive-MS/MS

“…The main chemical constituents of TSD include alkaloids (from RALP), phenolic acids and saponins (from RGP), and volatile oils (from RZ). At present, chemical composition [ 10 ], pharmacological, pharmacokinetic [ 11 , 12 , 13 ], and metabolomics [ 8 , 9 , 14 ] studies have been preliminarily conducted on TSD, especially on its cardiovascular activities. Most of the studies on TDS concentrated on the pharmacokinetics of diterpene alkaloids after oral administration of TDS, and some of the studies focused on the changes in the in vivo metabolome or lipidome profile against myocardial ischemia, heart failure, hypothyroidism.…”