Investigating herb–herb interactions: The potential attenuated toxicity mechanism of the combined use of Glycyrrhizae radix et rhizoma (Gancao) and Sophorae flavescentis radix (Kushen)

Ethnopharmacological relevance Glycyrrhizae radix et rhizoma (Gancao) is often prescribed together with Sophorae flavescentis radix (Kushen) in traditional Chinese medicinal practice to increase the efficacy on the treatment of hepatitis and hepatic fibrosis . Meanwhile, long-term single used Gancao can cause adverse reactions, lead to pseudohypercorticosteroidism especially. But the side effects of Gancao are significantly reduced when combined with Kushen; the reasons are still unknown. The aim of this study was to elucidate potential pharmacokinetic interaction between Kushen and Gancao, and to provide guidance for clinical medicine safety. Materials and methods A specific and rapid HPLC–MS method was established to quantify the four main activity ingredients matrine (MT), oxymatrine (OMT), glycyrrhizin (GL) and glycyrrhetinic acid (GA) in rat plasma. In this study, the pharmacokinetic parameters and the pharmacokinetic differences of the four main activity ingredients MT, OMT, GL and GA in single herb and Kushen–Gancao couple were obtained. Results Compared with oral administration of Gancao extract, K 10 and T max of GA significantly increased to 0.43   h −1 and 30   h after giving Kushen–Gancao ( p <0.05), but T 1/2 and V d were reduced to 0.73   L   kg −1 and 4.98   h ( p <0.05). In addition, the AUC of GA was increased, and the other three activity ingredients all decreased. Conclusion GA as the main factor leading to the sodium–water retention side effects of Gancao. The result found that the absorption of GA was significantly slowed down and the metabolism rate was accelerated in Kushen–Gancao than single herb. So the attenuated toxicity mechanism may be because the accumulation of GA reduced in vivo. The conclusion has important meaning to the compatibility of Chinese med.