The compatibility of six alkaloids in ermiao pill explored by comparative pharmacokinetic and network pharmacological study.

Ermiao pill (EMW), a traditional Chines medicine (TCM), composed of two herb pair phellodendri cortex (PC) and atractylodis rhizome (AR), used for the treatment of PID and inflammatory related diseases. However, the underlying mechanism was still margin. The compatibility played a crucial role in the complex drugs such as TCM, it wasn't well clear. Now we proposed a compositive strategy, which integrated pharmacokinetics and network pharmacology to explore the compatibility in EMW. Firstly, a simple, rapid, and selective method based on UPLC-MS/MS was established and validated for simultaneous qualification of six alkaloids in rat plasma, which was used for a comparative pharmacokinetic study of EMW and its constituted herb PC. The concentration-time profiles suggested that AR might reduce the toxicity of some alkaloids in EMW. Secondly, network pharmacology analysis showed that the key protein PTGS2 was targeted by four alkaloids, the competition among them might allevited by AR. Thirdly, molecular docking exhibited the interactions between the alkaloids and PTGS2 through H and π-πbonds, and the same residue formed interactions with different alkaloids, which account for the toxicity of these alkaloids, and these confirmed by the cell viability assay. Consequently, the combination of pharmacokinetics and network pharmacology clarified the compatibility in EMW.