P327 Evaluation of Transporter-Mediated Herb-Drug Interaction Potential of Berberine, Saikosaponin, and Glycyrrhizin

Da-Hyeon Choi , Pharmacology, Inje University College of Medicine, Busan, South Korea
Ho-Jung Shin , Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea
Min Hye Kim , Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea
Su Jeong Lim , Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea
Boram Kang , Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea
Jae-Gook Shin , Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea
Im-Sook Song , Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea
Herbal medicines and their active ingredients are widely used worldwide, and they have become an important part of clinical medicine. However, the combined use of herbs and drugs has increased the possibility of pharmacokinetic and pharmacodynamic interactions. To determine the underlying mechanisms of transporter-mediated herb-drug interaction, we investigated the inhibitory effects of berberine, saikosaponin A, and glycyrrhizin on the functions of organic cation transporter1 (OCT1), organic anion transporter1 (OAT1), and organic anion transporting polypeptide1B1 (OATP1B1), and evaluated the interaction potential of berberine, saikosaponin A, and glycyrrhizin with substrate drugs for these transporters. Berberine (10 mM) and saikosaponin A (20 mM) inhibited the uptake of MPP+ by 70-99% in oocytes expressing OCT1. However, glycyrrhizin did not affect on OCT1-mediated MPP+ uptake. The Ki values for berberin and saikosaponin A on OCT1-mediated MPP+ uptake were 0.047±0.033 mM and 3.1±0.3 mM, respectively. Glycyrrhizin (100 mM) and saikosaponin A (20 mM), but not berberine, inhibited the OATP1B1-mediated uptake of estron-3-sulfate by 80-90% and the Ki values for glycyrrhizin and saikosaponin A on OATP1B1-mediated estrone-3-sulfate uptake were 16.63±4.2 mM and 7.2±3.2 mM, respectively. In case of OAT1, there were no interactions with berberine, saikosaponin A, and glycyrrhizin. In conclusion, berberine, saikosaponin A, and glycyrrhizin, major constituent in antispasmodic herbal medicine, showed differential interaction potential for OAT1, OCT1, and OATP1B1 transporters. Among them, berberine showed potent inhibitory potential for OCT1 with no effect on OAT1 and OATP1B1 function. Saikosaponin A had an inhibitory effect on both OCT1 and OATP1B1 activity and glycyrrhizin had moderate inhibitory potential for OATP1B1.