Chitosan nanoparticles encapsulated Piper betle essential oil alleviates Alzheimer's disease associated pathology in Caenorhabditis elegans

A multifaceted approach in treating Alzheimer's disease (AD), a neurodegenerative condition that poses health risks in the aging population is explored in this investigation via encapsulating Piper betle essential oil (PBEO) in chitosan nanoparticles (ChNPs) to improve solubility and efficacy of PBEO. PBEO-ChNPs mitigated AD-like features more effectively than free PBEO by delaying paralysis progression and reducing serotonin hypersensitivity, ROS levels, Aβ deposits, and neurotoxic Aβ-oligomers in the Caenorhabditis elegans AD model. PBEO-ChNPs significantly improved lifespan, neuronal health, healthspan, cognitive function, and reversed deficits in chemotaxis and reproduction. PBEO-ChNPs also induced stress response genes daf-16, sod-3, and hsp-16.2. The participation of the DAF-16 pathway in reducing Aβ-induced toxicity was confirmed by daf-16 RNAi treatment, and upregulation of autophagy genes leg-1, unc-51, and bec-1 was noted. This study is the first to demonstrate an alternative biopolymeric nanoformulation with natural PBEO and chitosan, in mitigating AD and its associated symptoms.