Neuroprotective role of Diosgenin, a NGF stimulator, against Aβ (1–42) induced neurotoxicity in animal model of Alzheimer’s disease

Abstract

Diosgenin is a neurosteroid derived from the plants and has been previously reported for its numerous health bene cial 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, neuroin ammation 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.

Kolaviron neuroprotective effect against okadaic acid-provoked cognitive impairment

“…In the current research, we preferred to have a pretreatment, preventive, and neuroprotective strategy and not a post-treatment and restorative design and accordingly we administered kolaviron before okadaic acid microinjection. Such design for Alzheimer's-like phenotype and under neurotoxic conditions is according to literature [ [68] , [69] , [70] , [71] ]. However, as a limitation, it is recommended to evaluate the beneficial and restorative effect of kolaviron post-treatment in OA model of AD like phenotype in future studies.…”

Research progress of natural products and their derivatives against Alzheimer’s disease

“…It is an important raw material for the synthesis of steroid hormone drugs such as cortisone. Diosgenin protected a rat model of AD from Aβ1-42-induced neurotoxicity 68 . Diosgenin was found to reduce heat shock homologs in Aβ-induced injury in 5XFAD mice 69 , HSC70 belongs to the family of heat shock proteins and can promote neuronal axonal degeneration and pathology in the brain of AD patients when expressed at high levels 70 , Τhus, effectively inhibiting HSC70 as a new target for the treatment of AD ( Figure 11 ).…”

Anti-Neuroinflammatory Potential of Natural Products in the Treatment of Alzheimer’s Disease

“…It is reported that DG can inhibit the NF-κB pathway by regulating upstream receptors such as TLRs and downstream mediators including iNOS and COX-2 in LPS-stimulated RAW 264.7 macrophages [ 200 , 201 ]. Another study showed that DG could improve memory impairment in an AD model of Aβ1-42-stimulated mice by stimulating NGF to regulate the ACh-mediated cholinergic-anti-inflammatory pathway and also inhibiting the TLR/NF-κB pathway [ 202 ].…”