Potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting efflux transporter P-gp

In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple approaches. In silico and in vitro Caco-2 cell model were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-gp, as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration were investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo were altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine 123 (Rh 123) across Caco-2 cell monolayer further indicated that function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory...
Source: Journal of Pharmaceutical Analysis - Category: Drugs & Pharmacology Source Type: research