SMTP-44d の可用性エポキシドヒドロラーゼ阻害作用を介した抗酸化作用および抗炎症作用メカニズムの検討

Abstract

We have previously reported the efficacy of SMTP-44D for diabetic neuropathy (DN) through its potential antioxidant and anti-inflammatory activities. However, the mechanisms underlying the antioxidant and antiinflammatory activities of SMTP-44D remain unclear. The present study aimed to reveal the mechanism of these effects of soluble epoxide hydrolase (sEH) inhibition by SMTP-44D. In the in vivo assay, SMTP-44D (30 mg/kg) was administered to 200 mg/kg streptozotocin (STZ)-induced diabetic mice from the 8 to the 28 days after the injection of STZ. In the in vitro assay, IMS32 cells were incubated in a high glucose medium for 48 h and then treated with SMTP-44D (30 μM) for 48 h. The effects of the ratio of epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), oxidative stress markers, and inflammatory factors by administration of SMTP-44D were assessed by LC-MS/MS, TBARS, and ELISA assay, respectively. Furthermore, apoptosis was evaluated by TUNEL assay. SMTP -44D treatment considerably increased the ratio of EETs to DHETs and mitigated oxidative stress, inflammation, and apoptosis. These results suggested that SMTP-44D can suppress the induction of apoptosis by exerting antioxidant and anti-inflammatory effects, possibly through sEH inhibition. SMTP-44D can be a potential therapeutic agent against DN.