Title:Neuroprotective Effects of Fenugreek Leaf Extract in a Drosophila Model of Alzheimer's Disease Expressing Human Aβ-42
Volume: 22
Issue: 8
Author(s): Himanshi Varshney, Kajal Gaur, Iqra Subhan, Javeria Fatima, Smita Jyoti, Mantasha I, Mohd. Shahid, Rahul and Yasir Hasan Siddique*
Affiliation:
- Department of Zoology, Faculty of Life Sciences, Laboratory of Alternative Animal Models, Section of Genetics, Aligarh
Muslim University, Aligarh, 202002, Uttar Pradesh, India
Keywords:
Alzheimer’s disease, fenugreek, oxidative stress, Aβ-42, metabolomics, Drosophila, human Aβ-42.
Abstract:
Introduction: Much emphasis has been given to the biological activities of Fenugreek
against various diseased conditions. This study investigated the effect of fenugreek leaf extract on
behavioural and cognitive function of transgenic Drosophila having human Aβ-42 expression in the
neurons, herein referred as Alzheimer’s disease model flies (AD flies).
Methods: AD flies were exposed to four different doses of fenugreek leaf extract (FE) containing
i.e., 0.005, 0.010, 0.015 and 0.02 g/ml for 30 days. Thereafter, behavioural and cognitive assessment
was done using climbing ability, activity pattern, aversive phototaxis and odour choice indexes.
The life span of different groups of flies was also recorded. The effect of FE on the oxidative
stress markers, acetylcholinesterase, monoamine oxidase (MAO) and caspase 3 and 9 activities
were determined. The deposition of Aβ-42 aggregates in the brain tissue of the flies was studied by
performing immunostaining. Also, the metabolic profile of different groups of flies was studied by
performing LC-MS/MS. Compared with control flies, 22 selected metabolites were found to be upregulated
and downregulated among transgenic AD flies and FE exposed AD flies compared to
control.
Results: The findings of this study showed the neuroprotective role of fenugreek extract, which
could be employed for the treatment of Alzheimer’s disease. The AD flies exposed to FE showed a
dose-dependent postponement in the decline of climbing ability, activity and cognitive impairments.
A significant dose dependent increase in the life span was also noticed in the AD flies exposed
to FE. A significant reduction in the oxidative stress, acetylcholinesterase, monoamine oxidase,
and caspase-3&9 activities was also observed in a dose dependent manner. The results obtained
from the immunostaining suggest the reduction in the deposition of Aβ-42 fibril, which was
also confirmed by the docking studies showed the energetically favoured interaction useful for inhibiting
the acetylcholinesterase and Aβ-42 aggregates.
Discussion: This study demonstrates the neurological potency of fenugreek leaf extract (FE) in a
Drosophila model of AD due to its antioxidantive, anti-cholinesterase, and neuroprotective properties.
Using a combination of behavioral, biochemical, histological, and metabolomic approaches,
we evaluated the therapeutic potential of FE in mitigating AD-like symptoms in transgenic flies expressing
Aβ-42.
Conclusion: Fenugreek leaf extract may serve as a potential natural remedy for slowing down or
alleviating the progression of AD.
