Ya Zhao1#, Fuwen Xiao2#, Qiaohong Hu2* and Ruizhi Zhao1,3*
1Second Affiliated Hospital, Guangzhou University of Chinese Medicine, China
2School of Pharmacy, Guangdong Pharmaceutical University, China
3Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, China #These authors are equally contributed to this work
Natural products become the focus of modern researchers for developing Pgp inhibitors to Multidrug Resistant (MDR) reverse of Hepatocellular Carcinoma (HCC). Micromolecular Hydrophilic Extract from vinegar baked radix bupleuri (MHE) was reported to inhibit Pgp expression in vitro Pgpover expressing cells. In this paper, we studied the effect of MHE on the in vivo behavior of Pgp substrate digoxin to explore its prospect of clinical application as a Pgp inhibitor. Concentrations of digoxin in plasma and tissues were determined by UPLC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration–time data by using non-compartmental analysis. The changes of tissue distribution were evaluated by Relative Uptake Efficiency (RUE) and Relative Targeting Efficiency (RTE). The Pgp and Oatp2 mRNA expression in different tissues were determined by qRT-PCR. MHE dose-dependently reduced AUC (0-t), AUC (0-∞), MRT (0-t) of digoxin, and increased its level of CLz/F in rats plasma (P<0.01, P<0.05). MHE increased RUE of digoxin in liver, but decreased RUE of digoxin in small intestine and plasma. MHE hampering liver Pgp mRNA expression was the main reason of liver-targeting effect. MHE is a potent Pgp inhibitor for multidrug-resistant HCC in clinic for its effect of inhibiting Pgp expression in vivo and its liver targeting effect.
Micromolecular hydrophilic extract; Vinegar baked radix bupleuri; Pgp inhibitor; Liver-targeting effect; Multidrug resistant; Hepatocellular carcinoma
Zhao Y, Xiao F, Hu Q, Zhao R. Micromolecular Hydrophilic Extract from Vinegar Baked Radix Bupleuri Affecting Digoxin Distribution by Selectively Inhibiting Pgp Expression. Ann Pharmacol Pharm. 2022;7(1):1204..