Inhibition of Human Cytochrome P450 2C8-catalyzed Amodiaquine N-desethylation: Effect of Five Traditionally and Commonly Used Herbs

Background

In Southeast Asia and many parts of the world, herbal products are increasingly used in parallel with modern medicine.

Objective

This study aimed to investigate the effects of herbs commonly used in Southeast Asia on activity of cytochrome P450 2C8 (CYP2C8), an important human hepatic enzyme in drug metabolism.

Materials and Methods

The selected herbs, such as Eurycoma longifolia Jack (ELJ), Labisia pumila (LP), Echinacea purpurea (EP), Andrographis paniculata (AP), and Ginkgo biloba (GB), were subjected to inhibition studies using an in vitro CYP2C8 activity marker, amodiaquine N-desethylase assay. Inhibition parameters, inhibitory concentration 50% (IC₅₀), and K_i values were determined to study the potency and mode of inhibition.

Results

All herbs inhibited CYP2C8 with the following order of potency: LP > ELJ > GB > AP > EP. LP and ELJ inhibited potently at K_i’s of 2 and 4 times the K_i of quercetin, the positive control. The inhibition by LP was uncompetitive in nature as compared to competitive or mixed type inhibition observed with other herbs. GB exhibited moderate inhibitory effect at a K_i 6 times larger than quercetin K_i. AP and EP, on the other hand, showed only weak inhibition.

Conclusion

The herbs we chose represented the more commonly used herbs in Southeast Asia where collision of tradition and modernization in healthcare, if not properly managed, may lead to therapeutic misadventures. We conclude that concurrent consumption of some herbs, in particular, LP and ELJ, may have relevance in drug-herb interactions via CYP2C8 inhibition in vivo.