Effects of huperzine A on liver cytochrome P-450 in rats.
OBJECTIVE
To predict possible drug interaction and assure safety medication of huperzine A (HupA).


METHODS
The effects of HupA on activities and expressions of cytochrome P-450 (CYP) were examined. Liver microsomes and total mRNA were prepared from rats treated orally with 0, 0.1 (pharmacological dose), 1, or 2 mg/kg huperzine A for 2 weeks. Phenobarbital, 3-methylcholanthrene (3-MC), ethanol, and dexamethasone were used as positive controls. Total CYP protein was assayed by carbon monoxide difference spectrum. Activity of isoenzyme was detected with specific probe. Expression of CYP protein and mRNA was analyzed with Western blot and RT-PCR.


RESULTS
No changes of isoenzyme expression and catalytic activities were found in rats treated with 0.1 mg/kg huperzine A. Huperzine A 1, 2 mg/kg parallelly increased CYP1A2 activity, protein and mRNA, although they were minor when contrasted with 3-MC. Huperzine A 1, 2 mg/kg got no effects on CYP2C11, CYP2B1/2, 2E1 and 3A.


CONCLUSIONS
Activity and expression of liver CYP isoenzymes were not affected in rats treated with pharmacological dose of HupA, but HupA at toxicological dose may elicit a slight inductive response of CYP1A2. The CYP1A2 induction produced by HupA is related to transcription enhancement.
Ma
Xiao-Chao
XC
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Wang
Hai-Xue
HX
Xin
Jian
J
Zhang
Ting
T
Tu
Zeng-Hong
ZH
D000470:Alkaloids; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004305:Dose-Response Relationship, Drug; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*; D039181:Steroid 16-alpha-Hydroxylase / Q000378:metabolism
D000470:Alkaloids; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D012717:Sesquiterpenes; C050426:huperzine A; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D019388:Cytochrome P-450 CYP1A2; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase