2. Academic Validation
  3. Searching the cytochrome p450 enzymes for the metabolism of meranzin hydrate: a prospective antidepressant originating from Chaihu-Shugan-San

Searching the cytochrome p450 enzymes for the metabolism of meranzin hydrate: a prospective antidepressant originating from Chaihu-Shugan-San

  • PLoS One. 2014 Nov 26;9(11):e113819. doi: 10.1371/journal.pone.0113819.
Xi Huang 1,  Ying Guo 2,  Wei-Hua Huang 2,  Wei Zhang 2,  Zhi-Rong Tan 2,  Jing-Bo Peng 2,  Yi-Cheng Wang 2,  Dong-Li Hu 2,  Dong-Sheng Ouyang 2,  Jian Xiao 3,  Yang Wang 3,  Min Luo 3,  Yao Chen 1
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, China.
PMID: 25427198 DOI: 10.1371/journal.pone.0113819
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.

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