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

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.