Oleanolic acid alleviates oxidative stress in Alzheimer's disease by regulating stanniocalcin-1 and uncoupling...

Oxidative stress is thought to play an important role in the occurrence and development of Alzheimer's disease (AD) and antioxidants may delay or even treat AD. Oleanolic acid (OA) exhibits antioxidant properties against many diseases. However, its effects on oxidative stress in AD remain unclear. Here, we explored the role and mechanism of action of OA in N2a/APP695swe cells exposed to oxidative stress. The cells were incubated with different concentrations of OA (0, 5, 8, 10, 15, and 25 μmol/L) for 24 hours. Higher concentrations of OA (10, 15, and 25 μmol/L) significantly suppressed the apoptosis, caspase-3 activity, reactive oxygen species level, and β amyloid (Aβ) content and increased the viability of these cells. OA (10 μmol/L) also increased the expression of stanniocalcin-1 (STC-1) and uncoupling protein-2 (UCP2) in N2a/APP695swe cells. STC-1 interference markedly reversed the effect of OA on UCP2, indicating that OA may regulate UCP2 expression in N2a/APP695swe cells via STC-1. Moreover, UCP2 inhibition significantly reversed the OA-mediated effects on cell viability, caspase-3 activity, reactive oxygen species, and Aβ level. Thus, OA regulates UCP2 expression via STC-1 to alleviate oxidative stress and Aβ level in N2a/APP695swe cells.