title: Potential risk of mulberry-drug interaction: modulation on P-glycoprotein and cytochrome P450 3A.
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 (AUC(0-540)) and the maximum blood concentration (Cmax) of CSP by 53.2 and 65.8%, respectively. Repeated dosing of mulberry significantly decreased the AUC(0-540) 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.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan, Republic of China.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Hsu
authors.forename: Chi-Sheng
authors.initials: CS
authors.lastname: Shia
authors.forename: Shiuan-Pey
authors.initials: SP
authors.lastname: Lin
authors.forename: Pei-Dawn Lee
authors.initials: PD
authors.lastname: Chao
authors.forename: Shin-Hun
authors.initials: SH
authors.lastname: Juang
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005638:Fruit / Q000737:chemistry; D041743:Herb-Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D031625:Morus / Q000737:chemistry*; D059808:Polyphenols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D059808:Polyphenols; D016572:Cyclosporine; D051544:Cytochrome P-450 CYP3A