Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.
School of Chemistry and Chemical and Engineering, Guangxi Minzu University, Nanning 530008, China.
Molecules. 2023 May 8;28(9):3964. 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.
细胞内 tau 聚集是阿尔茨海默病 (AD) 和其他 tau 病的标志性病理学特征。tau 蛋白在高度磷酸化形式下是 AD 中双螺旋丝 (PHFs) 和神经原纤维缠结 (NFTs) 的组成部分。阻止 tau 聚集和/或磷酸化是目前治疗 AD 的一种有前途的策略。在这里，我们阐明了槲皮素-3-O-新橙皮糖苷，一种源自非洲万寿菊（）的天然化合物，可以抑制 tau 聚集，并减少体外与多种疾病相关的 tau 磷酸化。此外，还通过口服给药在 P301S-tau 转基因小鼠中评估了 quercetagitrin 的体内作用。该化合物治疗恢复了小鼠的认知缺陷和神经元丢失。该化合物还防止了 NFTs 的形成和小鼠海马体和皮质中 tau 的磷酸化。此外，quercetagitrin 的喂养通过抑制 NF-κB 激活在小鼠中显示出神经炎症保护作用。总之，我们的数据表明，槲皮素-3-O-新橙皮糖苷具有进一步开发为 AD 和其他 tau 病治疗药物的潜力。
