Abstract
Diosgenin is a neurosteroid derived from the plants and has been previously reported for its numerous health beneficial properties, such as anti-arrhythmic, hypolipidemic, and antiproliferative effects. Although several studies conducted earlier suggested cognition enhancement actions of diosgenin against neurodegenerative disorders, but the molecular mechanisms underlying are not clearly understood. In the present study, we investigated the neuroprotective effect of diosgenin in the Wistar rats that received an intracerebroventricular injection of Amyloid-β (1–42) peptides, representing a rodent model of Alzheimer’s disease (AD). Animals were treated with 100 and 200 mg/kg/p.o of diosgenin for 28 days, followed by Amyloid-β (1–42) peptides infusion. Animals were assessed for the spatial learning and memory by using radial arm maze and passive avoidance task. Subsequently, animals were euthanized and brains were collected for biochemical estimations and histopathological studies. Our results revealed that, diosgenin administration dose dependently improved the spatial learning and memory and protected the animals from Amyloid-β (1–42) peptides induced disrupted cognitive functions. Further, biochemical analysis showed that diosgenin successfully attenuated Amyloid-β (1–42) mediated plaque load, oxidative stress, neuroinflammation and elevated acetylcholinesterase activity. In addition, histopathological evaluation also supported neuroprotective effects of diosgenin in hippocampus of rat brain when assessed using hematoxylin–eosin and Cresyl Violet staining. Thus, the aforementioned effects suggested protective action of diosgenin against Aβ (1–42) induced neuronal damage and thereby can serve as a potential therapeutic candidate for AD.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- 1,25D3–MARRS:
-
1,25D3 -membrane-associated, rapid response steroid-binding protein
- ACh:
-
Acetylcholine
- AChE:
-
Acetylcholinesterase
- aCSF:
-
Artificial cerebrospinal fluid
- AD:
-
Alzheimer’s disease
- Akt:
-
Protein kinase B
- ANOVA:
-
Analysis of variance
- AP:
-
Anterior–posterior
- Aβ:
-
Amyloid beta
- BFCN:
-
Basal forebrain cholinergic neurons
- CAT:
-
Catalase
- CMC:
-
Carboxymethyl cellulose
- CV:
-
Cresyl violet
- DTNB:
-
5,5-dithio-bis-(2-nitrobenzoic acid)
- DV:
-
Dorsal-ventral
- EDTA:
-
Ethylenediamine tetraacetic acid
- ELISA:
-
Enzyme-linked Immune Sorbent Assay
- ERK:
-
Extracellular signal-regulated kinase
- GSR:
-
Glutathione reductase
- H&E:
-
Hematoxylin and eosin
- H2O2 :
-
Hydrogen peroxide
- i.c.v:
-
Intracerebroventricular
- IAEC:
-
Institutional Animal Ethics Committee
- IL-6:
-
Interleukin 6
- JNK:
-
c-Jun N-terminal kinase
- MAPK:
-
Phosphorylated-p38 mitogen activated protein kinase
- ML:
-
Medial-lateral
- NADH:
-
Nicotinamide adenine dinucleotide
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- NF-κB:
-
Nuclear factor kappa B
- NGF:
-
Nerve growth factor
- p75NTR:
-
p75 pan neurotrophin receptor
- PI3K:
-
Phosphatidylinositol 3-kinase
- RAM:
-
Radial arm maze
- ROS:
-
Reactive oxygen species
- SD:
-
Standard deviation
- SOD:
-
Superoxide dismutase
- TLR:
-
Toll-like receptor
- TNF-α:
-
Tumour necrosis factor
- TrkA:
-
Tyrosine kinase A receptor
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Acknowledgements
We express our gratitude to the Department of Pharmacognosy and Phytochemistry, Department of Pharmacology and Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, Ooty for providing various chemicals and facilities used during the course of the study. This project was financially supported by the Lady Tata Memorial Trust, Mumbai, India with senior research fellowship (SRF).
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SS performed the experiments and was a major contributor in writing the manuscript. JA analyzed and interpreted the raw data regarding the Alzheimer’s disease. SP conceptualized, reviewed and edited the manuscript. SPD reviewed and edited the manuscript. All authors read and approved the final manuscript.
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All experiments were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (National Research Council (US)) and was approved by the Institutional Animal Ethics Committee (IAEC) (JSSCP/IAEC/PhD/Pharmacy Practice/01/2018–19).
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Som, S., Antony, J., Dhanabal, S. et al. Neuroprotective role of Diosgenin, a NGF stimulator, against Aβ (1–42) induced neurotoxicity in animal model of Alzheimer’s disease. Metab Brain Dis 37, 359–372 (2022). https://doi.org/10.1007/s11011-021-00880-8
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DOI: https://doi.org/10.1007/s11011-021-00880-8