Short term treatment with St. John's wort, hypericin or hyperforin fails to induce CYP450 isoforms in the Swiss Webster mouse.
This investigation was designed to determine whether St. John's wort (SJW)(435 mg/kg/d), a readily available antidepressant, or its purported active constituents hypericin (1 mg/kg/d) and hyperforin (10 mg/kg/d) were able to induce various hepatic cytochrome P450 (CYP450) isoforms. SJW, hypericin and hyperforin were administered to male Swiss Webster mice for four consecutive days and hepatic microsomes were prepared on day 5. None of the three treatments resulted in a statistical change in total hepatic CYP450 (SJW treated 0.95 +/- 0.09 nmol/mg vs control 1.09 +/- 0.14 nmol/mg). Furthermore, the catalytic activities of CYP1A2. CYP2E1 and CYP3A were unchanged from control following all three treatments as determined by ethoxyresorufin O-deethylation, p-nitrophenol hydroxylation and erythromycin N-demethylation respectively. Additionally, western immunoblotting demonstrated that there was no significant change in the polypeptide levels of any of the three isoforms. These results indicate that four days of treatment with moderate to high doses of SJW, hyperforin or hypericin fails to induce these CYP450 isoforms in the male Swiss Webster mouse.
Bray
B J
BJ
Department of Pharmacology, University of Otago, Dunedin, New Zealand.
Brennan
N J
NJ
Perry
N B
NB
Menkes
D B
DB
Rosengren
R J
RJ
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000873:Anthracenes; D000928:Antidepressive Agents; D001835:Body Weight / Q000187:drug effects; D001643:Bridged Bicyclo Compounds; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D020902:Hypericum; D007527:Isoenzymes; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010696:Phloroglucinol / Q000031:analogs & derivatives; D028321:Plant Preparations / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology*
D000873:Anthracenes; D000928:Antidepressive Agents; D001643:Bridged Bicyclo Compounds; D007527:Isoenzymes; D028321:Plant Preparations; D013729:Terpenes; D010569:Perylene; C004965:hypericin; D003577:Cytochrome P-450 Enzyme System; D010696:Phloroglucinol; D000410:Alanine Transaminase; C001654:hyperforin