Jatamansinol from Nardostachys jatamansi (D.Don) DC. Protects Aβ42-Induced Neurotoxicity in Alzheimer's Disease Drosophila Model

Nardostachys jatamansi (D. Don) DC. is an essential plant used in Indian Ayurveda to treat neurological disorders, and it enhances memory. Its active phytochemical(s) responsible for neuroprotection is not yet studied. One of the neurological disorders, namely Alzheimer's disease (AD) causes dementia, is not having pharmacological strategies to effectively prevent the onset of AD, cure or reverse AD progression, and treat cognitive symptoms. Here is an attempt to analyze the neuroprotective effect of jatamansinol isolated from N. jatamansi against Aβ42 protein-induced neurotoxicity using the Aβ42 protein expressed Drosophila Alzheimer's disease (AD) model. Oregon-K (OK) and AD flies were reared on regular or jatamansinol supplemented food and analyzed for their lifespan, locomotor activity, learning and memory, eye degeneration, oxidative stress levels, antioxidant activities, cholinesterase activities, Aβ42 protein, and Aβ42 gene expression. Jatamansinol extends the lifespan, improves locomotor activity, enhances learning and memory, and reduces Aβ42 protein levels in AD flies. Jatamansinol boosts the antioxidant enzyme activities, prevents Aβ42 protein-induced oxidative stress, ameliorates eye degeneration, and inhibits cholinesterase activities in the AD model. This study evidences the protective effect of jatamansinol against the Aβ42 protein-induced neurotoxicity in the AD Drosophila model, suggesting its possible therapeutic potential against AD. [Display omitted] •Jatamansinol is a pyranocoumarin present in Nardostachys jatamansi.•It increases lifespan and improves memory and climbing ability in amyloid flies.•Jatamansiol protects the eye degeneration in amyloid flies.•It prevents oxidative stress and boosts anti-oxidant enzymes in amyloid flies.•Jatamansinol inhibits the choline esterase enzymes in the amyloid flies.