Potential risk of mulberry-drug interaction: Modulation on P-glycoprotein and cytochrome P450 3A

Pei Wen Hsu, Chi Sheng Shia, Shiuan Pey Lin, Pei Dawn Lee Chao, Shin Hun Juang*, Yu Chi Hou

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

24 Scopus citations

Abstract

Mulberry is a fruit containing polyphenol antioxidants. Cyclosporine (CSP), a potent immunosuppressant with a narrow therapeutic range, is widely used in transplant patients. This study investigated the effect of co-administration of mulberry on the bioavailability of CSP, a probe drug of P-glycoprotein (P-gp)/cytochrome P450 3A4 (CYP 3A4), in rats and relevant mechanisms. CSP (2.5 mg/kg) was orally administered with and without a single dose or the seventh dose of mulberry (2 g/kg) to rats. The results showed that a single dose of mulberry significantly decreased the area under the curve of concentration (AUC0-540) and the maximum blood concentration (Cmax) of CSP by 53.2 and 65.8%, respectively. Repeated dosing of mulberry significantly decreased the AUC0-540 and Cmax of CSP by 23.7 and 39.7%, respectively. Mechanism studies indicated that mulberry significantly increased the activities of P-gp and CYP 3A. In conclusion, mulberry significantly reduced the bioavailability of CSP through activating the functions of P-gp and CYP 3A.

Original languageEnglish
Pages (from-to)4464-4469
Number of pages6
JournalJournal of Agricultural and Food Chemistry
Volume61
Issue number18
DOIs
StatePublished - 08 05 2013
Externally publishedYes

Keywords

  • Cyclosporine
  • P-glycoprotein
  • cytochrome P450 3A
  • mulberry

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