Evaluation of the Antioxidant and Anti-Alzheimer’s Activity of Oleanolic Acid: An In-vitro Study

Introduction: Alzheimer’s Disease (AD) is a neurodegenerative condition characterised by cognitive decline and memory loss, with oxidative stress and neuroinflammation playing key roles in its pathology. While traditional treatments primarily focus on managing symptoms and slowing disease progression, there is a growing recognition of the need for alternative treatment methods. Oleanolic Acid (OA), a natural triterpenoid, has shown neuroprotective and antioxidant properties. Aim: To assess the effects of OA in reducing oxidative stress and targeting major pathological features of AD, including amyloidbeta plaque accumulation and tau hyperphosphorylation. Materials and Methods: The present in-vitro study was conducted in the Centre for Global Health Research, Saveetha Medical College and Hospitals, Chennai, Tamil Nadu, India, from May 2024 to June 2024. AD models were used to assess OA’s impact on oxidative stress levels and amyloidbeta plaque formation. A series of in-vitro assays, such as the 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assay, the 2,2′- azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and the Lipid Peroxidase (LPO) inhibition assay, were performed to evaluate the antioxidant properties of OA. The Acetylcholinesterase (AChE) inhibition assay, amyloid (Aβ 1-42) aggregation inhibition assay, and β-secretase inhibition assay were performed to assess the anti-alzheimer effects of OA. A two-way Analysis of Variance (ANOVA) test was used to assess the differences between means, and the Holm-Sidak test was used to compare the means with the standard group. Results: OA significantly reduced oxidative stress and demonstrated a strong antioxidant effect by scavenging free radicals and inhibiting the LPO enzyme, almost on par with ascorbic acid. At a concentration of 320 μM, OA exhibited an antioxidising effect comparable to that of ascorbic acid. It also decreased amyloid-beta plaque formation in AD models, inhibited AChE at the same level as donepezil at higher concentrations, and inhibited the β-secretase enzyme on par with donepezil at lower concentrations, thereby indicating its strong anti-alzheimer potential. Conclusion: In the present study, OA showed promising antioxidant and anti-alzheimer effects, suggesting its potential as a therapeutic agent for AD. By reducing oxidative stress and addressing key pathological features of the disease, OA may contribute to managing and slowing the progression of Alzheimer’s disease. Further studies are necessary to confirm its therapeutic potential in clinical settings.