Zederone Improves the Fecal Microbial Profile in Dementia Induced Rat Model: A First Report

Abstract

Background: Dementia correlates with Alzheimer’s disease, Parkinson’s disease, frontotemporal and cerebrovascular diseases. There are supporting shreds of evidence on the pharmacological activity of curcuma caesia (Zingiberaceae family) for its antioxidant, antidepressant, analgesic, anticonvulsant, and anti-acetylcholinesterase effect. Objective: This study aims to analyze the fecal microbial profile in Zederone treated demented rat model. Method: In our study, isolation and characterization of Zederone were carried out from curcuma caesia rhizomes, followed by estimation of its memory-enhancing effect on Aluminium-induced demented rat, which was evaluated by behavioural study on radial 8 arm maze. Moreover the detection of amyloid plaque formation was carried out using fluorescent microscopy of the congo red-stained rat brain tissues of the cerebral neocortex region. This study included eighteen female Wistar Albino rats that were divided into three groups that consisted of six rats in each group. The study of fecal microbial profile by metagenomic DNA extraction followed by next-generation sequencing was carried out to establish the correlation between gut microbes and amyloid plaques in dementia. Results: Zederone could be characterized as pale yellow colored, needle-shaped crystals with 96.57% purity. This compound at 10 mg/kg body weight showed cognition improving capacity (p ≤ 0.0001) with a reduction of accumulated amyloid plaques that were detected in the demented group in fluorescence microscope and fecal microbiome study divulged an increased shift towards Lactobacillus genera in the treated group from Bacteroides in the demented group. Conclusion: This sesquiterpenoid compound would assist in the modulation of gut bacterial dysbiosis and act as a better therapeutic drug for dementia and other neurological disorders.