Studies on the Incompatibility between and Based on the P-gp.

and are an incompatible herbal pair in the traditional Chinese medicine theory "eighteen incompatible medicaments," and they should not be used simultaneously in clinical treatment for safety. This study aimed to investigate the incompatibility mechanism between and based on their interaction with P-glycoprotein (P-gp). The interaction between and during decocting as well as absorption was investigated by determining the dry extract yield and by rat single-pass intestinal perfusion (SPIP) model. Inhibition of different species of on P-gp function was examined using the SPIP model. The mRNA and protein expression of P-gp was determined by PCR and western blotting. The active ingredients of were predicted and screened for inhibiting P-gp activity by Schrodinger's molecular docking and MDR1-MDCK cell transport study, respectively. Mediation of monoester alkaloids in by P-gp was predicted and examined using Schrodinger's molecular docking and SPIP experiment, respectively. In the results, when was combined with , the toxic ingredient benzoylmesaconine in displayed higher intestinal permeability, whereas the toxic ingredients showed no significant difference during the decoction process. inhibited both the P-gp function and expression; in contrast, inhibited the function only. Alkaloids including peimine, peimisine, and imperialine were the active ingredients for inhibiting P-gp activity. Benzoylmesaconine in was the substrate of P-gp.