In Vitro and In Silico Studies of Soluble Epoxide Hydrolase Inhibitors from the Roots of Lycopus lucidus
Open Access
- 13 February 2021
- Vol. 10 (2), 356
- https://doi.org/10.3390/plants10020356
Abstract
Soluble epoxide hydrolase (sEH) is an enzyme that is considered a potential therapeutic target in human cardiovascular disease. Triterpenes (1–4) and phenylpropanoids (5–10) were isolated from Lycopus lucidus to obtain sEH inhibitors through various chromatographic purificationtechniques. The isolated compounds were evaluated for their inhibitory activity against sEH, and methyl rosmarinate (7), martynoside (8), dimethyl lithospermate (9) and 9″ methyl lithospermate (10) showed remarkable inhibitory activity, with the IC50 values ranging from 10.6 ± 3.2 to 35.7 ± 2.1 µM. Kinetic analysis of these compounds revealed that 7, 9 and 10 were competitive inhibitors bound to the active site, and 8 was the preferred mixed type inhibitor for allosteric sites. Additionally, molecular modeling has identified interacting catalytic residues and bindings between sEH and inhibitors. The results suggest that these compounds are potential candidates that can be used for further development in the prevention and treatment for cardiovascular risk.Keywords
Funding Information
- National Research Foundation of Korea Grant funded by the Korean Government (NRF-2019R1A6A1A03031807)
This publication has 33 references indexed in Scilit:
- Soluble Epoxide HydrolaseArteriosclerosis, Thrombosis, and Vascular Biology, 2012
- Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertensionAmerican Journal of Physiology-Renal Physiology, 2009
- Role of Soluble Epoxide Hydrolase in Postischemic Recovery of Heart Contractile FunctionCirculation Research, 2006
- Cardiovascular Therapeutic Aspects of Soluble Epoxide Hydrolase InhibitorsCardiovascular Drug Reviews, 2006
- Soluble epoxide hydrolase is a therapeutic target for acute inflammationProceedings of the National Academy of Sciences of the United States of America, 2005
- Distribution of Soluble Epoxide Hydrolase and of Cytochrome P450 2C8, 2C9, and 2J2 in Human TissuesJournal of Histochemistry & Cytochemistry, 2004
- The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activityProceedings of the National Academy of Sciences of the United States of America, 2003
- Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension.Hypertension, 2002
- Pathways of Epoxyeicosatrienoic Acid Metabolism in Endothelial CellsOnline Journal of Public Health Informatics, 2001
- Soluble Epoxide Hydrolase Regulates Hydrolysis of Vasoactive Epoxyeicosatrienoic AcidsCirculation Research, 2000