title: Searching the cytochrome p450 enzymes for the metabolism of meranzin hydrate: a prospective antidepressant originating from Chaihu-Shugan-San.
abstract: Meranzin hydrate (MH), an absorbed bioactive compound from the Traditional Chinese Medicine (TCM) Chaihu-Shugan-San (CSS), was first isolated in our laboratory and was found to possess anti-depression activity. However, the role of cytochrome P450s (CYPs) in the metabolism of MH was unclear. In this study, we screened the CYPs for the metabolism of MH in vitro by human liver microsomes (HLMs) or human recombinant CYPs. MH inhibited the enzyme activities of CYP1A2 and CYP2C19 in a concentration-dependent manner in the HLMs. The Km and Vmax values of MH were 10.3±1.3 µM and 99.1±3.3 nmol/mg protein/min, respectively, for the HLMs; 8.0±1.6 µM and 112.4±5.7 nmol/nmol P450/min, respectively, for CYP1A2; and 25.9±6.6 µM and 134.3±12.4 nmol/nmol P450/min, respectively, for CYP2C19. Other human CYP isoforms including CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 showed minimal or no effect on MH metabolism. The results suggested that MH was simultaneously a substrate and an inhibitor of CYP1A2 and CYP2C9, and MH had the potential to perpetrate drug-drug interactions with other CYP1A2 and CYP2C19 substrates.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China; Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Tan
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Peng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Hu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Ouyang
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya road, Changsha, Hunan 410078, China; Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000928:Antidepressive Agents / Q000378:metabolism* / Q000494:pharmacology; D003374:Coumarins / Q000378:metabolism* / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010936:Plant Extracts / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C497000:chaihu-shugan-san; C508408:meranzin hydrate; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6