Abstract
Simple SummaryMangostanaxanthone IV (MX-IV) is a major constituent in Garcinia mangostana. It induced neuro-protective effects in the ICV-STZ mouse model through diminishing ICV-STZ-induced oxidative stress, neuro-inflammation, and apoptosis which was reflected by a significant reduction in malondialdehyde (MDA), hydrogen peroxide (H2O2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) brain contents contrary to increased glutathione (GSH) content. It also decreased amyloid plaques’ number and phosphorylated tau expression via the PI3K/Akt/GSK-3β pathway.Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by amyloid deposition and neurofibrillary tangles formation owing to tau protein hyperphosphorylation. Intra-cerebroventricular (ICV) administration of streptozotocin (STZ) has been widely used as a model of sporadic AD as it mimics many neuro-pathological changes witnessed in this form of AD. In the present study, mangostanaxanthone IV (MX-IV)-induced neuro-protective effects in the ICV-STZ mouse model were investigated. STZ (3 mg/kg, ICV) was injected once, followed by either MX-IV (30 mg/kg/day, oral) or donepezil (2.5 mg/kg/day, oral) for 21 days. Treatment with MX-IV diminished ICV-STZ-induced oxidative stress, neuro-inflammation, and apoptosis which was reflected by a significant reduction in malondialdehyde (MDA), hydrogen peroxide (H2O2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) brain contents contrary to increased glutathione (GSH) content. Moreover, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase content and cleaved caspase-3 activity were reduced together with a marked decrement in amyloid plaques number and phosphorylated tau expression via PI3K/Akt/GSK-3β pathway modulation, leading to obvious enhancement in neuronal survival and cognition. Therefore, MX-IV is deemed as a prosperous nominee for AD management with obvious neuro-protective effects that were comparable to the standard drug donepezil.
Highlights
Alzheimer’s disease (AD), a neurodegenerative disease with increasing prevalence with age, is portrayed by progressive cognitive dysfunction [1]
ICV-STZ injected mice which received either mangostanaxanthone IV (MX-IV) or donepezil showed significant amelioration in the mean escape latency (MEL) on days 2, 3, and 4 with no significant difference between the treated groups
ICV-STZ group revealed an obvious decrease in the time spent in the target quadrant, whereas it was markedly increased in treated ICV-STZ groups
Summary
Alzheimer’s disease (AD), a neurodegenerative disease with increasing prevalence with age, is portrayed by progressive cognitive dysfunction [1]. Neuro-inflammation, insulin resistance, and synaptic failure along with amyloid-beta (Aβ) deposition and tau hyperphosphorylation are involved in the pathogenesis of sporadic AD (SAD), the most prevalent form of AD [2]. Studies have shown that ICV-STZ injection was accompanied by oxidative stress, glial activation, spatial memory impairments in addition to tau hyperphosphorylation, and Aβ deposition [4,5]. Oxidative stress is reported to play a crucial role in AD pathology and progression as it contributes to Aβ aggregation and tau hyperphosphorylation which provokes further redox imbalance [6]. Oxidative stress and neuro-inflammation are deemed as key players in Aβ deposition and tau hyperphosphorylation which are the main hallmarks associated with AD [8]. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most vital pathways for neuronal survival and it is involved in neuro-inflammation [9]
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