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 200mg/kg/p.o of diosgenin for 28days, 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.
Highlights
Alzheimer’s disease (AD) is the most prevalent, complex and devastating neurodegenerative disorder in the aging population and clinically characterized by gradual erosion of cognitive functions, decline in perception and language ability, personality disturbance, inability of self-care and death from opportunistic infections (Souza et al 2016).Basal forebrain cholinergic neurons (BFCNs) are considered to be prime neurons responsible for learning, memory, and attention, through acetylcholine (ACh) innervation (Baxter et al 1999)
We investigated the neuroprotective effect of diosgenin in the wistar rats that received an intracerebroventricular injection of Amyloid-β [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42] peptides, representing a rodent model of Alzheimer’s disease (AD)
The present work strongly suggests neuroprotective property of diosgenin which was in accordance with the available evidences against AD
Summary
Alzheimer’s disease (AD) is the most prevalent, complex and devastating neurodegenerative disorder in the aging population and clinically characterized by gradual erosion of cognitive functions, decline in perception and language ability, personality disturbance, inability of self-care and death from opportunistic infections (Souza et al 2016).Basal forebrain cholinergic neurons (BFCNs) are considered to be prime neurons responsible for learning, memory, and attention, through acetylcholine (ACh) innervation (Baxter et al 1999). Abnormal formation of intracellular neurofibrillary tangles and extracellular deposition of amyloid beta (Aβ) peptides in the AD brain displayed neuritic atrophy and loss of synapses in BFCNs. Degeneration of BFCNs act as one of the major pathological diagnostic hallmark of AD and is severely affected due to disruption of communication with target neurons in the hippocampus and cortex (Fahnestock et al 2019). Degeneration of BFCNs act as one of the major pathological diagnostic hallmark of AD and is severely affected due to disruption of communication with target neurons in the hippocampus and cortex (Fahnestock et al 2019) With the age, these affects gets worsen leading to the cascade of pathogenic events causing neuroinflammation, glutamate excitotoxicity, metal dyshomeostasis, oxidative stress and mitochondrial dysfunction in specific parts of the brain (Souza et al 2016; Lian et al 2017). Accumulated Aβ, in AD pathology, in turn causes degeneration of BFCNs and enhances Aβ production by regulating p75NTR over-expression, NGF-induced signalling transduction and internalization of NGF receptors (Zhang et al 2013)
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