The protective roles of Eugenol on type 1 diabetes mellitus through NRF2 mediated oxidative stress pathway

Abstract

Type 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia caused by damage to the pancreatic β cells and an absolute insulin deficiency, which will affect multiple organs and has a poor prognosis. Oxidative stress and apoptosis play a major role in the progression of T1DM. Eugenol (EUG) is a natural compound with anti-inflammatory, anti-oxidant, and anti-apoptosis activities. However, the potential effects of EUG on T1DM had not been investigated. In this study, we established the streptozotocin (STZ)-induced T1DM mouse model in vivo and STZ-induced pancreatic β cell MIN6 cell model in vitro to explore the protective effects of EUG on T1DM, and tried to illuminate the potential mechanism. Our results showed that EUG intervention could activate the expression of nuclear factor E2-related factor 2 (NRF2), increase the expressions of downstream proteins NQO-1 and HO-1 regulated by NRF2, alleviate pancreatic β cell damage in T1DM, elevate insulin secretion, and reduce the expression levels of apoptosis and oxidative stress related markers. Furthermore, these effects of EUG could be significantly reversed by ML385, an inhibitor of NRF2. The present study suggested that EUG exerted protective effects on pancreatic β cells in T1DM by mitigating apoptosis and oxidative stress through activating the NRF2 signaling pathway. Consequently, EUG holds great promise as a potential therapeutic candidate for T1DM.