Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple approaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (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 was 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 was 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 the 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 effect, which helps clarify the compatibility rationale of these two herbs.

乌头-甘草对草药被广泛用于减轻毒性和增强附子的功效。在这项研究中，通过使用多种方法研究了草药对的潜在协同机制。使用计算机和体外Caco-2细胞模型研究甘草中存在的生物活性成分与P-糖蛋白（P-gp）的潜在结合模式，以及对P-gp的抑制作用。此外，还研究了乌头碱（AC）与甘草的活性成分结合的抗炎活性，以及​​共同给药后AC的药代动力学模式。与甘草的生物活性成分（10 mg / kg）联合使用时，AC（1 mg / kg）对大鼠的抗炎作用增强。同时，就Cmax和AUC而言，体内AC的暴露发生了改变。例如，当与liquiritigenin组合使用时，Cmax和AUC分别增加到1.9倍和1.3倍。电脑研究表明，P-gp具有面向外构象的潜在结合方式。从若丹明-123（Rh-123）跨Caco-2细胞单层转运获得的数据进一步表明，P-gp的功能受到甘草中化学物质的抑制。因此提出协同作用归因于甘草对P-gp的抑制，因为已经证明AC是P-gp的底物。结果表明，Wu头-甘草对的潜在协同作用机制是通过抑制关键外向转运蛋白P-gp的功能来增强系统循环中AC的暴露，并具有抗炎作用，这有助于阐明它们的相容性原理。两种草药。