Quercetagitrin Inhibits Tau Accumulation and Reverses Neuroinflammation and Cognitive Deficits in P301S-Tau Transgenic Mice

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 9; p. 3964
• Main Authors: Zhong, Suyue, Ye, Jinwang, Deng, Yunsong, Zhang, Mohan, Zou, Miaozhan, Yao, Xuanbao, Xiao, Shifeng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.05.2023; MDPI
• Subjects: Accumulation; Advertising executives; Alzheimer Disease - metabolism; Alzheimer's disease; Animal cognition; Animals; Antibodies; Brain; Cognition; Dementia; Disease Models, Animal; Filaments; Flavonoids; Genetic engineering; gliosis; Inflammation; Kinases; memory; Mice; Mice, Transgenic; Neurofibrillary tangles; Neuroinflammatory Diseases; Neurons; NF-κB protein; Oral administration; Pathology; Phosphorylation; Proteins; quercetagitrin; Tau protein; tau Proteins - genetics; tau Proteins - metabolism; Tauopathies - metabolism; Transgenic animals; Transgenic mice; United Kingdom; Massachusetts; China; Germany; memory; gliosis; inflammation; tau protein; quercetagitrin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28093964

Intracellular tau accumulation is a hallmark pathology of Alzheimer's disease (AD) and other tauopathies. Tau protein, in the hyperphosphorylated form, is the component of paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) in AD. Blocking tau aggregation and/or phosphorylation is currently a promising strategy for AD treatment. Here, we elucidate that quercetagitrin, a natural compound derived from African marigold ( ), could inhibit tau aggregation and reduce tau phosphorylation at multiple disease-related sites in vitro. Moreover, the in vivo effect of quercetagitrin was assessed in P301S-tau transgenic via oral administration. The compound treatment restored the cognitive deficits and neuron loss in the mice. The formation of NFTs and tau phosphorylations in the hippocampus and cortex of the mice was also prevented by the compound. Moreover, quercetagitrin feeding displayed neuroinflammation protection through the inhibition of NF-κB activation in the mice. Together, our data reveal that quercetagitrin possesses the potential to further develop as a therapeutic medicine for AD and other tauopathies.