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

Abstract

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.

Virtual Screening of Nrf2 Dietary-Derived Agonists and Safety by a New Deep-Learning Model and Verified In Vitro and In Vivo

“…After Nrf2 agonist activity and toxicity screening, pesticides and drugs were removed manually, and 169 compounds were selected as potential Nrf2 agonists. Literature review results showed that 32 out of the 169 compounds in the list had clear evidence of Nrf2 agonistic activity and were mainly focused on compounds with high predictive indices (>0.85), demonstrating the accuracy of the predictive model − (Table ).…”

Oleanolic Acid Acetate Alleviates Cisplatin-Induced Nephrotoxicity via Inhibition of Apoptosis and Necroptosis In Vitro and In Vivo

“…OA treatment induced apoptosis in osteosarcoma cells, a process regulated by Bcl-2 and caspase-3 through inhibition of the Notch signaling pathway [ 46 ]. In contrast, OA had protective effects in neuronal cells, ameliorating oxidative stress and neuronal apoptosis by inhibiting the Nrf2/HO-1 pathway [ 47 ]. These studies suggest that OA has protective effects on normal cells and anti-tumor effects on cancer cells.…”

Integrative transcriptome and single-cell sequencing technology analysis of the potential therapeutic benefits of oleanolic acid in liver injury and liver cancer

“…Numerous studies have found oleanolic acid to have good antioxidant effects in many diseases. In common brain tissue injury, oleanolic acid can activate the expression of antioxidant stress enzymes through the Nrf2/HOMX1 pathway, thereby down-regulating ROS in injured brain tissue in subarachnoid hemorrhage and achieving the function of protecting brain tissue [ 7 ]. In diabetes, oleanolic acid can reduce cellular oxygen stress through agonism of the Akt and MAPK pathways, thereby inhibiting the effects of insulin resistance during diabetes treatment [ 8 ].…”