title: Aloe activated P-glycoprotein and CYP 3A: a study on the serum kinetics of aloe and its interaction with cyclosporine in rats.
abstract: Aloe, the leaf juice of Aloe vera, is a popular functional food worldwide. The major constituents of aloe are polyphenolic anthranoids such as aloin, aloe-emodin and rhein. Cyclosporine (CSP), an immunosuppressant with a narrow therapeutic window, is a probe substrate of P-glycoprotein (P-gp), an efflux pump, and CYP 3A4. This study first investigated the serum kinetics of aloe, then evaluated the modulation effects of aloe on P-gp and CYP 3A through an aloe-CSP interaction study in rats. The serum kinetic study showed that aloe-emodin glucuronides (G) and rhein sulfates/glucuronides (S/G) were major molecules in the bloodstream. The aloe-CSP interaction study showed that the systemic exposure to CSP was significantly decreased by either a single dose or multiple doses of aloe. The results of in vitro studies indicated that aloe activated P-gp and aloe metabolites activated CYP 3A4. In conclusion, aloe ingestion activated the functions of P-gp and CYP 3A in rats.
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan 404, Republic of China. hou5133@gmail.com splin@mail.cmu.edu.tw.
authors.forename: Meng-Syuan
authors.initials: MS
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan 404, Republic of China.
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan 404, Republic of China.
authors.forename: Ching-Ya
authors.initials: CY
authors.lastname: Huang
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan 404, Republic of China. hou5133@gmail.com splin@mail.cmu.edu.tw.
authors.forename: Pei-Dawn Lee
authors.initials: PL
authors.lastname: Chao
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan 404, Republic of China. hou5133@gmail.com splin@mail.cmu.edu.tw.
authors.forename: Shiuan-Pey
authors.initials: SP
authors.lastname: Lin
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan 404, Republic of China. hou5133@gmail.com splin@mail.cmu.edu.tw and Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan 404, Republic of China.
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*; D000504:Aloe / Q000737:chemistry*; D000818:Animals; D000880:Anthraquinones / Q000097:blood / Q000737:chemistry; D016572:Cyclosporine / Q000097:blood* / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010936:Plant Extracts / Q000097:blood* / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000880:Anthraquinones; D010936:Plant Extracts; D016572:Cyclosporine; C518327:aloe emodin; D051544:Cytochrome P-450 CYP3A; C020491:rhein