Jatamansinol from Nardostachys jatamansi Ameliorates Tau-Induced Neurotoxicity in Drosophila Alzheimer's Disease Model.

Abstract

Nardostachys jatamansi has long been used to prepare Medhya Rasayana in traditional Indian Ayurveda medicine to treat neurological disorders and enhance memory. Jatamansinol from the N. jatamansi against Alzheimer's disease (AD) showed that it could be a multitargeted drug against AD. Drosophila is an ideal model organism for studying a progressive age-related neurodegenerative disease such as AD since its neuronal organizations and functioning are highly similar to that of humans. The current study investigates the neuroprotective properties of jatamansinol against Tau-induced neurotoxicity in the AD Drosophila model. Results indicate jatamansinol is not an antifeedant for larva and adult Drosophila. Lifespan, locomotor activity, learning and memory, Tau protein expression level, eye degeneration, oxidative stress level, and cholinesterase activities were analyzed in 10, 20, and 30-day-old control (wild type), and tauopathy flies reared on jatamansinol supplemented food or regular food without jatamansinol supplementation. Jatamansinol treatment significantly extends the lifespan, improves locomotor activity, enhances learning and memory, and reduces Tau protein levels in tauopathy flies. It boosts the antioxidant enzyme activities, prevents Tau-induced oxidative stress, ameliorates eye degeneration, and inhibits cholinesterase activities in Tau-induced AD model. This study provides the first evidence that jatamansinol protects against Tau's neurotoxic effect in the AD Drosophila model, and it can be a potential therapeutic drug candidate for AD.