Oleanolic acid reduces oxidative stress and neuronal apoptosis after experimental subarachnoid hemorrhage by regulating Nrf2/HO-1 pathway.

Oxidative stress is an early major pathological feature after subarachnoid hemorrhage (SAH) and involves in the development of acute brain injury, neuronal apoptosis and cerebral vasospasm following SAH. Antioxidant stress is an effective way to improve the prognosis of SAH. Oleanolic acid is a widely used triterpenoid from plants, which has strong antioxidant activities, hepatoprotective, anti-inflammatory and anti-cancer activities. However, whether oleanolic acid exerts its anti-oxidant effect after SAH and the underlying mechanisms involved in it is unclear. In current study, the SAH model was established on Sprague Dawley rats using a standard intravascular puncture model. We found OA treatment significantly reduced malondialdehyde levels, and increased the levels of superoxide dismutase, catalase and GSH-Px after SAH, and reduced many EBI-related indicators, including brain edema, BBB disruption, SAH grades, and neurological score. In addition, the activation of Nrf2/HO-1 pathway after SAH was also detected. And by using Nrf2 siRNA intracerebroventricular injections, apoptosis related factors downstream of Nrf2/HO-1 pathway were detected. By TUNEL staining, OA treatment obviously reduced neuronal apoptosis. Therefore, we suggest that OA could alleviate oxidative stress and reduce neuronal apoptosis through activating Nrf 2/HO-1 pathway.