Esculetin Ameliorates Cognitive Impairments in D‑Galactose‑Induced Alzheimer’s Disease Rats by Inhibiting Inflammation and Oxidative Stress

Background: Alzheimer disease (AD) is a common form of dementia and is described by memory loss and behavioral disorder. The prevalence of AD is increasing rapidly each year worldwide. Objectives: In this study, we aimed to discover the therapeutic properties of esculetin against D‑galactose (D‑gal)‑induced AD in an animal model. Materials and Methods: AD was initiated in rats by administering 150 mg/kg of D‑gal via subcutaneous route for 6 weeks and supplemented with 10, 20, and 30 mg/kg of esculetin, respectively. Subsequently, memory and learning of the rats were investigated using the Morris water maze (MWM). The organ index of the liver, spleen, thymus, and kidneys was assessed. The enzyme activities of superoxide dismutase (SOD), catalase (CAT), GSH‑Px, and heme oxygenase‑1 (HO‑1) and the levels of advanced glycation end products (AGEs), 8‑iso‑prostaglandin F (8‑iso‑PGF), and 8‑hydroxy‑2‑deoxyguanosine (8‑OHdG) were assessed using commercially available kits. The level of acetylcholine (Ach) and the activity of acetylcholinesterase (AChE) was also assessed using kits. The brain tissue samples were assessed microscopically. Results: According to the results, esculetin significantly improved the bodyweight and organ index in AD animals. It significantly modulated the spatial learning and memory and improved the activities of CAT, SOD, GSH‑Px, and HO‑1. It significantly reduced the contents of AGEs, 8‑iso‑PGF, and 8‑OHdG and inflammatory markers. Furthermore, esculetin increased the level of ACh and the reduced activity of AChE. Histological analysis of the brain tissue revealed that esculetin attenuated the D‑gal‑induced histological changes in the brain of AD rats. Conclusion: The findings of this study reveal that esculetin can ameliorate inflammation and oxidative damage in D‑gal‑induced AD rats. It can be further explored as a therapeutic agent to treat AD.