Calycosin Influences the Metabolism of Five Probe Drugs in Rats

Abstract

Background

Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb Astralagusmembranaceus (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases.

Aim

The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism.

Methods

Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Results

No significant differences were observed for omeprazole and midazolam, compared to the control group. T_max and t_1/2 values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group (T_max h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). C_max of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, P<0.001).

Conclusion

Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.

Keywords:

• calycosin
• herb-drug interactions
• UPLC-MS/MS
• cocktail
• CYP450

Acknowledgment

This work was financially supported by grants from Jinhua City public welfare projects (No.2017-4-049).

Disclosure

The authors have no conflicts of interest to declare.