title: [Effects of isorhamnetin on CYP3A4 and herb-drug interaction].
abstract: The study is to report the investigation of the effects of isorhamnetin on CYP3A4 and herb-drug interaction. A reporter gene assay is used to test pregnane X receptor transactivation action, qRT-PCR and a luminescence-based assay were applied to determine mRNA induction and enzyme activity of CYP3A4 after isorhamnetin treatment. The interaction of irinotecan and isorhamnetin was assessed by inhibition assay of cell proliferation. Isorhamnetin at 1, 10 and 25 micromol x L(-1) transactivated the CYP3A4 reporter construct and upregulated CYP3A4 mRNA as well in a dose-dependent manner. However, isorhamnetin had no effect on enzyme activity of CYP3A4 and irinotecan HepG2 cytotoxicity. In conclusion, activation of PXR by isorhamnetin played a role in the upregulation of CYP3A4 mRNA. Moreover, joint action of isorhamnetin with other drugs may not be associated with the herb-drug interaction.
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicine and Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Ding
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Dou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D000077146:Irinotecan; D000077297:Pregnane X Receptor; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; C047368:3-methylquercetin; D000077146:Irinotecan; D011794:Quercetin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002166:Camptothecin