Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 98, Issue -, Pages 526-534Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2017.02.023
Keywords
Cimicifuga dahurica; Ranunculaceae; Cycloartane-type triterpenoids; Soluble epoxide hydrolase; Molecular docking
Funding
- Priority Research Center Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology, Republic of Korea [2009-0093815]
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In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that an ethanolic extract of the roots of Cimicifuga dahurica (Turcz.) Maxim. significantly inhibits sEH in vitro. A phytochemical study on the dichloromethane fraction of C. dahurica resulted in the isolation of two new cycloartane triterpenoids (1 and 6), together with 13 known cycloartane analogues (2-5 and 7-15). The structures of compounds were determined by spectroscopic methods. All of the triterpenoid derivatives inhibited sEH enzymatic activity in a concentration-dependent manner, and 13 of the tested compounds showed significant activity. Among them, compounds 1, 3, 5, 7, 9, and 12 showed the highest levels of inhibitory activity, with IC50 values of about 5 mu M or less. Kinetic analysis of compounds 1, 3, 5-9, 11, 12, and 14 revealed that compounds 3, 6, 7, 11, and 14 were non-competitive; 1, 5, 9, and 12 were mixed-type; and 8 was a competitive inhibitor. Furthermore, in silico molecular docking indicated that compounds 3, 6-9, 11, 12, and 14 bound to sEH in a similar manner and had stable binding energies, as calculated by AutoDock 4.2 and processed in a 10,000-ps molecular dynamics simulation to assess the binding stability of compounds 5, 7, and 9. (C) 2017 Elsevier B.V. All rights reserved.
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