The role of soluble epoxide hydrolase and its inhibitors in depression

Evidence suggests that around 30 ​% of patients with depression do not respond to antidepressant treatment, with most of them having sub-chronic levels of inflammation. Soluble epoxide hydrolases (sEH) are enzymes present in all living organisms, which metabolize cytochrome P (CYP)-derived epoxy fatty acids to their corresponding diols. Accumulating evidence suggests that sEH plays a key role in the anti-inflammatory properties exerted by the metabolism of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). Crucial evidence demonstrates that protein expression of sEH in the brain of mice experiencing depressive-like behaviour, as well as in patients with major depressive disorder is higher than in controls. Of note, treatment with sEH inhibitors exert anti-inflammatory, neurogenic and antidepressant-like effects in pre-clinical models of depression. In this review, the author discusses the role of sEH in the metabolism of ω-3 PUFAs in the context of depression, and the clinical value of sEH inhibitors as alternative therapeutic strategies for patients suffering from this condition.