Inhibition of Cytochrome P450 Activities by Extract and Its Prenylated Flavonoids in Human Liver Microsomes.

Authors:
Daeun Yim
Daeun Yim
Inje University College of Medicine
Min Jung Kim
Min Jung Kim
Severance Hospital
South Korea
Su-Jun Lee
Su-Jun Lee
Inje University College of Medicine
South Korea
Jae Gook Shin
Jae Gook Shin
Inje University Busan Paik Hospital
Dong Hyun Kim
Dong Hyun Kim
Biomedical Research Institute

Evid Based Complement Alternat Med 2019 13;2019:2673769. Epub 2019 Mar 13.

Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan 614-735, Republic of Korea.

possesses several pharmacological properties and has been widely used for the treatment of diarrhea, inflammation, abscess, dysentery, and fever in East Asian countries. is a major source of prenylated flavonoids, such as sophoraflavone and kushenol. In this study, we examined the effects of extract and its prenylated flavonoids on cytochrome P450 (CYP) isoform activity in human liver microsomes. The extract inhibited CYP2C8, CYP2C9, CYP2C19, and CYP3A activities, with IC values of 1.42, 13.6, 19.1, and 50 g/mL, respectively. CYP2B6 was only inhibited in human liver microsomes preincubated with the extract. CYP3A4 was more strongly inhibited by the extract in the presence of NADPH, suggesting that the extract may inhibit CYP2B6 and CYP3A4 via mechanism-based inactivation. Prenylated flavonoids also inhibited CYP isoforms with different selectivity and modes of action. Kushenol I, leachianone A, and sophoraflavone G inhibited CYP2B6, whereas kushenol C, kushenol I, kushenol M, leachianone A, and sophoraflavone G inhibited CYP3A4 via mechanism-based inhibition. Our results suggest that may contribute to herb-drug interactions when coadministered with drugs metabolized by CYP2B6, CYP2C8, CYP2C9, and CYP3A4.

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/2673769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436327PMC
March 2019
1 Read

Publication Analysis

Top Keywords

prenylated flavonoids
16
liver microsomes
12
human liver
12
sophoraflavone inhibited
8
leachianone sophoraflavone
8
cyp3a4 mechanism-based
8
kushenol leachianone
8
extract prenylated
8
kushenol kushenol
8
cytochrome p450
8
cyp2c8 cyp2c9
8
extract
6
inhibited
6
kushenol
5
microsomes preincubated
4
cyp2b6 inhibited
4
inhibited human
4
preincubated extract
4
extract cyp3a4
4
extract presence
4

References

(Supplied by CrossRef)

2010
Article in Evid Based Complement Alternat Med
Evid Based Complement Alternat Med 2015

Similar Publications