Moscatilin Ameliorates Tau Phosphorylation and Cognitive Deficits in Alzheimer’s Disease Models

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease and a common cause of dementia, manifesting as progressive memory loss and cognitive decline. Moscatilin, which reportedly reduces fever and is anti-inflammatory, is the bibenzyl extract from Dendrobium loddigesii. This study aimed to examine whether moscatilin ameliorates tau phosphorylation and cognitive deficits in AD models. The first in vitro AD-like model was developed by cotransfection with the pCAX FLAG APP and pRK5-EGFP-Tau P301L plasmids, resulting in the neuronal overexpression of amyloid precursor protein (APP) and tau P301L, a tauopathy-associated tau. The second model was developed by using okadaic acid to induce tau protein phosphorylation. Spatial memory/cognition was assessed using water maze and elevated plus maze tests in a scopolamine-induced mouse model, and brain slices were evaluated further by immunohistochemistry (IHC). Moscatilin significantly reduced phospho-tau expression in a concentration-dependent manner, decreased tau aggregation, and reduced apoptosis. These results indicated that moscatilin reversed tauopathy through GSK3β inactivation and inhibition of oxidative stress. Furthermore, in vivo data demonstrated that moscatilin ameliorated learning and memory impairments in mice, while IHC and Western blot results of the mouse brain confirmed that moscatilin decreased tau phosphorylation. Our novel findings suggest that moscatilin has neuroprotective effects against AD.

Anti-Inflammatory and Tau Phosphorylation–Inhibitory Effects of Eupatin

“…Patients with AD have reduced tau phosphatase activity, most of which is caused by PP2A [6]. OA has been identified as a potent PP2A activity inhibitor that can induce AD-like tau hyperphosphorylation in vitro and in vivo [16,33]. Our prior research revealed the occurrence of significant tau phosphorylation in Neuro-2a cells that were given OA or transfected with the pRK5-EGFP-Tau P301L plasmid, which encodes human mutant P301L-tau [32].…”

A Bibenzyl Component Moscatilin Mitigates Glycation-Mediated Damages in an SH-SY5Y Cell Model of Neurodegenerative Diseases through AMPK Activation and RAGE/NF-κB Pathway Suppression

“…( Figure 6 ). Although moscatilin possesses the ability to facilitate tau phosphorylation in an in vitro Alzheimer’s disease-like model developed by cotransfection with the amyloid precursor protein and tau-related plasmids, or is induced by okadaic acid, it cannot evaluate the effect of moscatilin on the mitigation of glycation mediated damages in neuronal cells [ 37 ]. Here, we provide evidence that moscatilin alleviates AGEs-induced mitochondrial dysfunction.…”

Anti-Inflammatory and Tau Phosphorylation–Inhibitory Effects of Eupatin

“…Patients with AD have reduced tau phosphatase activity, most of which is caused by PP2A [6]. OA has been identi ed as a potent PP2A activity inhibitor that can induce AD-like tau hyperphosphorylation in vitro and in vivo [32,33]. Our prior research revealed the occurrence of signi cant tau phosphorylation in Neuro-2a cells that were given OA or transfected with the pRK5-EGFP-Tau P301L plasmid, which encodes human mutant P301L-tau [33].…”

“…OA has been identi ed as a potent PP2A activity inhibitor that can induce AD-like tau hyperphosphorylation in vitro and in vivo [32,33]. Our prior research revealed the occurrence of signi cant tau phosphorylation in Neuro-2a cells that were given OA or transfected with the pRK5-EGFP-Tau P301L plasmid, which encodes human mutant P301L-tau [33]. The results of the present study revealed that eupatin signi cantly inhibited OA-or plasmid-induced tau phosphorylation at multiple sites.…”