Soluble Epoxide Hydrolase Inhibition in Liver Diseases: A Review of Current Research and Knowledge Gaps
Jeffrey Warner, Josiah Hardesty, Kara Zirnheld, Craig J. McClain, Dennis Warner, Irina Kirpich
Abstract
Emerging evidence suggests that soluble epoxide hydrolase (sEH) inhibition is a valuable therapeutic strategy for the treatment of numerous diseases, including those of the liver. sEH rapidly degrades cytochrome P450-produced epoxygenated lipids (epoxy-fatty acids), which are synthesized from omega-3 and omega-6 polyunsaturated fatty acids, that generally exert beneficial effects on several cellular processes. sEH hydrolysis of epoxy-fatty acids produces dihydroxy-fatty acids which are typically less biologically active than their parent epoxide. Efforts to develop sEH inhibitors have made available numerous compounds that show therapeutic efficacy and a wide margin of safety in a variety of different diseases, including non-alcoholic fatty liver disease, liver fibrosis, portal hypertension, and others. This review summarizes research efforts which characterize the applications, underlying effects, and molecular mechanisms of sEH inhibitors in these liver diseases and identifies gaps in knowledge for future research.