Integrative Medicine Insights
Synopsis: An open access, peer reviewed electronic journal that covers integration of complementary medicine into the over-all pursuit of patient health.
Indexing: 5 major databases. Pubmed indexing for NIH-funded research.
Processing time: Decision in 2 weeks for 90% of papers.
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Induction of Cytochrome P450 CYP3A by St John’s Wort in the Rat Liver and Intestine
Thuong Tran Phan1, See Huey Heng1, Damien Abarno1, Ross Allan McKinnon1 and Suong Ngoc Thi Ngo1,2
1Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia. 2School of Science and Primary Industries, Charles Darwin University, Casuarina Campus, Building 42, Darwin, NT 0909, Australia.
Abstract: It has been well reported that complementary medicines can significantly alter the way the body handles conventional drugs, leading to potential fatal herb-drug interactions. The aim of the present study was to investigate the molecular mechanism of drug interactions involving St John’s wort (SJW) (Hypericum perforatum L), a popular herbal medicine widely used for depression, particularly examining changes in the expression of cytochrome P450 CYP3A, the most abundant drug metabolising CYP enzymes in man.
Eighteen Sprague-Dawley (SD) rats were assigned randomly into 3 groups (n = 6/group): control, low dose and high dose (500 and 1000 mg/kg/day of SJW, equal to 1500 and 3000 μg/kg/day of Hypericin). Each group was treated with SJW or control preparation, by gastric gavage, for 14 consecutive days. Liver and intestinal CYP3A activity and protein and mRNA levels, from fi ve segments of the intestine, were examined using CYP3A-dependent erythromycin N-demethylation activity assay, quantitative immuno-blotting and real-time RT-PCR.
Increase in CYP3A activity and protein level by SJW was observed in some intestinal regions, with a 3.0 fold increase in liver CYP3A activity and a 10.6 fold increase in liver CYP3A1 mRNA (p 0.05) in a dose dependent manner. The results suggested that up regulation of liver CYP3A mRNA and differential induction of intestinal CYP3A play an important role in the molecular mechanism of herb-drug interactions.
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