title: Effects of huperzine A on liver cytochrome P-450 in rats.
abstract: 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.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiao-Chao
authors.initials: XC
authors.lastname: Ma
authors.forename: Hai-Xue
authors.initials: HX
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Xin
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Zeng-Hong
authors.initials: ZH
authors.lastname: Tu
mesh_terms: 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
chemical_list: 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