Modulation of cytochrome P450 1A2 and 3A4 by Morinda citrifolia (noni), Euterpe oleracea (acai), Lycium barbarum (goji) and Garcinia mangostana (mangosteen)

Abstract

The use of complementary and alternative medicine (CAM) including herbal products, for health maintenance and treatment of chronic diseases is continuously rising in the United States. Although considered safe due to their "natural" origin, herbal products are prone to herb‐drug interactions. Cytochrome (CYP) P450 enzymes are responsible for metabolizing xenobiotics including herbal products. The aim of our study was to investigate the effects of Morinda citrifolia (noni), Euterpe oleracea (açai), Lycium barbarum (goji) and Garcinia mangostana (mangosteen) on CYP1A2 and CYP3A4 activity using human cDNA‐expressed P450 enzymes and human hepatocytes. Açai and mangosteen significantly inhibited cDNA‐expressed CYP‐1A2 and ‐3A4 activities with IC50 values between 0.341% and 1.387% (v/v). In HepG2 cells, CYP‐1A2 and ‐3A4 activities were significantly inhibited after a four hour treatment with all juices, suggestive of direct effects on P450 protein. In contrast, CYP1A2 activity was maximally induced after a 10 h treatment, while CYP3A4 activity was inhibited after a 24 h treatment, suggesting effects at gene expression level. In primary human hepatocytes, CYP‐1A2 and ‐3A4 activities were maximally inhibited by açai and mangosteen. Our results indicate possible drug interactions with noni, açai, goji and mangosteen. USDA‐CREES (2004‐34135‐15182), NIH/NCMHD (P20MD000173‐06).

Herb-drug Interactions in Neuropsychiatric Pharmacotherapy – A Review of Clinically Relevant Findings

“…Extracts of noni have been shown to modulate the metabolic activities of multiple CYP isoforms. [ 120 , 121 ]. In a published report, Kang et al reported the case of a patient whose epilepsy has been managed with phenytoin for over 10 years without major side effects [ 33 ].…”