Abstract
Alzheimer’s disease (AD), which is among the most prevalent neurodegenerative diseases, manifests as increasing memory loss and cognitive decline. Tau phosphorylation and aggregation are strongly linked to neurodegeneration, as well as associated with chronic neuroinflammatory processes. The anti-inflammation effects of natural products have led to wide recognition of their potential for use in treating and preventing AD. This study investigated whether eupatin, a polymethoxyflavonoid found in Artemisia species, has inhibitory effects on neuroinflammation and tau phosphorylation. We treated mouse macrophages and microglia cells with lipopolysaccharides (LPSs) to activate inflammatory signals, and we treated neuronal cells with a protein phosphatase 2A inhibitor, okadaic acid (OA), or transfection with pRK5-EGFP-Tau P301L plasmid to induce tau phosphorylation. The results indicated that eupatin significantly reduced the LPS-induced protein expression and phosphorylation of p65 and inducible nitric oxide synthase as well as downstream products interleukin 6 and nitrite, respectively. Furthermore, eupatin markedly inhibited the expression of phospho-tau in response to OA treatment and plasmid transfection. We discovered that this inhibition was achieved through the inhibition of glycogen synthase kinase 3β (GSK3β), and molecular docking results suggested that eupatin can sufficiently bind to the GSK3β active site. Our results demonstrate that eupatin has neuroprotective effects, making it suitable for AD treatment.
Highlights
Alzheimer’s disease (AD) is a common progressive neurodegenerative disease and constitutes a global health concern
We evaluated the anti-inflammatory effect of eupatin and further determined whether eupatin can reduce tau phosphorylation to achieve neuroprotective effects against AD
We evaluated the cytotoxicity of other flavonoids, namely epigallocatechin-3-gallate (EGCG) and luteolin, in both cell types
Summary
Alzheimer’s disease (AD) is a common progressive neurodegenerative disease and constitutes a global health concern. 50 million people have dementia worldwide, and this number is expected to nearly triple by 2050 [1]. AD causes behavioral changes and continual degradation of mental function, resulting in functional decline in learning capacity [2]. The causes of AD are unknown, but oxidative stress and neuroinflammation have been identified as factors contributing to its pathogenesis [2]. Current drugs approved for AD treatment include acetylcholine esterase inhibitors and the N-methyl-d-aspartate receptor antagonist; these agents only provide. Molecules 2020, 25, 5652 symptomatic relief, and their benefits remain limited [3,4]. The development of new drugs for AD is urgently required
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