A new target for antidepressant drugs- soluble epoxide hydrolase

Soluble epoxide hydrolase (SEH) is a key enzyme involved in the metabolism of polyunsaturated fatty acids mediated by cytochrome P450 and is regarded as a marker of inflammation. SEH can exacerbate neuroinflammation, synaptic plasticity damage and liver-brain axis dysfunction by hydrolyzing epoxylated fatty acids (EpFAs) with neuroprotective effects. In recent years, the expression of SEH in the body has been found to be closely related to the development of depression accompanied by inflammation, but the pathological mechanism mediated by SEH is complex. Therefore, this article systematically analyzes the mechanism of action of SEH in the metabolic hubs of central astrocytes and peripheral liver, as well as the bidirectional regulatory mechanism in the central and peripheral regions. It also focuses on reviewing the rapid antidepressant effects achieved by SEH inhibitors through restoring EpFAs homeostasis, inhibiting inflammation, and activating signaling pathways such as brain-derived neurotrophic factor (BDNF) -neurotrophic tyrosine kinase receptor type 2 (TrkB). The synergistic mechanism of its combined treatment and the prospects of clinical transformation are also explored so as to provide a theoretical basis for the research and development of new antidepressant drugs targeting SEH.