👤 Awez Sikkalgar

Intracerebroventricular (ICV) streptozotocin (STZ) deveops Alzheimer's disease (AD)-like conditions in rodents, which are characterized by insulin resistance, tau pathology, and neurodegeneration. Hentriacontane, a natural compound found in various sources, including beeswax, possesses anti-inflammatory and antioxidant properties. In the present investigation, we performed in silico molecular docking, molecular dynamics, MMGBSA, PCA, and FEL analysis of hentriacontane and rivastigmine with acetylcholinesterase (AchE). Further, we assessed the in vivo neuroprotective effects of hentriacontane in an ICV-STZ-induced AD-like condition in rats. STZ (3 mg/kg/ICV) was injected into male Sprague-Dawley rats. Cognitive functions were evaluated by Barnes-Maze (BM), novel object recognition test (NORT), and passive avoidance test (PAT). Hentriacontane (3 and 5 mg/kg) and rivastigmine (1 mg/kg) were given intraperitoneally for 14 days. Brain-derived neurotrophic factor (BDNF), AchE, oxidative stress parameters including GSH, MDA, SOD, and CAT, and proinflammatory cytokines including IL-6, TNF-α, IL-1β, and NF-ҡB were measured via ELISA. Further, we have also estimated the BACE1 and NO levels. Histopathological evaluation was conducted using hematoxylin and eosin staining. In silico molecular docking, dynamics, and post-dynamics data revealed promising binding affinities of hentriacontane for AchE. Further, hentriacontane attenuated ICV-STZ-induced cognitive deficit in BM, NORT, and PAT. Additionally, altered oxidative stress, proinflammatory, and cell signalling parameters were restored. Histopathology revealed that the hentriacontane-treated group showed significant restoration of the small pyramidal cells in the CA1 and CA2 regions of the brain. Hentriacontane demonstrated neuroprotective effects by modulation of AchE, leading to improved cognitive functions as evidenced by in silico and in vivo investigations. Show less