Rustage_2025_Mol.Neurobiol__

Purpurin, a naturally occurring compound found in certain plants, has demonstrated promising neuroprotective effects in the context of Alzheimer's disease (AD). This study investigated the efficacy of purpurin in mitigating neurodegenerative changes induced by streptozotocin (3 mg/kg ICV) and amyloid beta (20 microM) in murine models. Neuroprotective effects were assessed through in vitro and in vivo experiments complemented by in silico simulation studies. SH-SY5Y cell viability, behavioral, biochemical, and histopathological studies were also conducted. The results revealed that purpurin interacts with acetylcholinesterase (AChE) and amyloid-beta (Abeta), exhibiting glide scores of - 10.72 and - 3.05 kcal/mol, respectively. Purpurin (8 microM) significantly alleviated Abeta-induced cellular damage by decreasing malondialdehyde production and enhancing superoxide dismutase and Thio barbituric acid reactive substances levels in a dose-dependent manner. Intraperitoneal administration of purpurin at 50 mg/kg significantly improved both long-term and short-term memory and enhanced social interactions. These benefits were linked to the reductions in AChE activity and oxidative and inflammatory marker levels triggered by streptozotocin. Neuroprotective effects were also supported by restoring neuronal DNA content in the hippocampus, cerebellum and prefrontal cortex. Histological findings further corroborated the reduction in neurodegenerative marker levels. In silico simulations supported these findings by indicating that purpurin primarily binds to the Trp 286 and Tyr 341 residues of AChE, inhibiting its catalytic activity at the peripheral anionic site. In conclusion, the neuroprotective activity of purpurin in AD models is attributed to its inhibitory effects on AChE, coupled with reductions in inflammation and oxidative stress and the restoration of neuronal DNA integrity in critical brain regions.