Effects of the total flavonoid extracts and the monomers of Daphne genkwa on CYP2C8 activity

Abstract

1. This study aimed to assess the effects of total flavonoid extracts (TFDG) and the monomers of Daphne genkwa on the CYP2C8 activity in vitro and in vivo.

2. The 50% inhibitory concentration (IC₅₀) values were used to determine the inhibitory effect of TFDG and its four monomers for the CYP2C8 activity by recombinant human CYP2C8 (RHCYP2C8) yeast microsome system in vitro, and the volume per dose index (VDI) was predicted the potential inhibition in vivo. The effects of multiple-dose administration of TFDG on the pharmacokinetic parameters of rosiglitazone in rats were evaluated.

3. The IC₅₀ values of apigenin, luteolin, hydroxy-genkwanin, genkwanin, and TFDG were 7.27 μmol/L, 11.9 μmol/L, 28.1 μmol/L, 127 μmol/L, and 13.4 μg/mL, respectively. The VDI values of apigenin and TFDG were 2.15 L and 6.60 L. In vivo study, compared with the control group, the elimination phase half-life and mean residence time in the TFDG treatment group were significantly increased by 96.9% and 106.8% (p <.05), respectively.

4. Apigenin showed a moderate inhibitory effect on the CYP2C8 activity in vitro, while the other three monomers were weak inhibitors. TFDG had a strong inhibitory effect on CYP2C8 in vitro and in vivo, and also inhibited the metabolism of rosiglitazone in rats.

Keywords:

• Daphne genkwa
• total flavonoid extract
• CYP2C8
• drug interactions
• apigenin

Disclosure statement

The authors report no declarations of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the ‘Natural science 2022 basic scientific research business fund cultivation project of China Pharmaceutical University’ (Project No. 3012200022).