Time-dependent Inhibition of CYP2C8 and CYP2C19 by Hedera helix Extracts, A Traditional Respiratory Herbal Medicine

Molecules

Seung Hyun Kim¹  Shaheed Ur Rehman²  In Sook Kim³  Min Sun Choi³  Hye Hyun Yoo³  Yonghui Zhang⁴ 

[1] College of Pharmacy, Yonsei Institute of Pharmaceutical Science, Yonsei University, Incheon 21983, Korea;Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 15588, Korea;School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China;

关键词: Hedera helix;    Araliaceae;    CYP inhibition;    human liver microsomes;    herb–drug interaction;   

DOI  :  10.3390/molecules22071241

来源: DOAJ

【 摘 要 】

The extract of Hedera helix L. (Araliaceae), a well-known folk medicine, has been popularly used to treat respiratory problems, worldwide. It is very likely that this herbal extract is taken in combination with conventional drugs. The present study aimed to evaluate the effects of H. helix extract on cytochrome P450 (CYP) enzyme-mediated metabolism to predict the potential for herb–drug interactions. A cocktail probe assay was used to measure the inhibitory effect of CYP. H. helix extracts were incubated with pooled human liver microsomes or CYP isozymes with CYP-specific substrates, and the formation of specific metabolites was investigated to measure the inhibitory effects. H. helix showed significant inhibitory effects on CYP2C8, CYP2C19 and CYP2D6 in a concentration-dependent manner. In recombinant CYP2C8, CYP2C19 and CYP2D6 isozymes, the IC50 values of the extract were 0.08 ± 0.01, 0.58 ± 0.03 and 6.72 ± 0.22 mg/mL, respectively. Further investigation showed that H. helix extract has a positive time-dependent inhibition property on both CYP2C8 and CYP2C19 with IC50 shift value of 2.77 ± 0.12 and 6.31 ± 0.25, respectively. Based on this in vitro investigation, consumption of herbal medicines or dietary supplements containing H. helix extracts requires careful attention to avoid any CYP-based interactions.

【 授权许可】

Unknown