Multifunctional Anti-Alzheimer's Disease Effects of Natural Xanthone Derivatives: A Primary Structure-Activity Evaluation

doi:10.3389/fchem.2022.842208

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	Multifunctional Anti-Alzheimer's Disease Effects of Natural Xanthone Derivatives: A Primary Structure-Activity Evaluation
	Hu, Xiaoyu; Liu, Chan; Wang, Kaichun; Zhao, Lanxue; Qiu, Yu; Chen, Hongzhuan; Hu, Jiangmiao; Xu, Jianrong
	2022
发表期刊	FRONTIERS IN CHEMISTRY
卷号	10 页码:842208
摘要	Background: A series of alpha-Mangostin (alpha-M) derivatives were designed and synthesized. alpha-M and four analogues were evaluated for their multifunctional anti-Alzheimer's disease (anti-AD) effects on fibrillogenesis, microglial uptake, microglial degradation, and anti-neurotoxicity of A beta, as well as LPS-induced neuroinflammation. The differences in bioactivities were analyzed to understand the structure-activity relationship for further modifications. Purpose: This study aims to investigate the anti-AD effects of alpha-M and elucidate its structure-activity relationship by comparing difference between alpha-M and several analogues. Methods: A beta fibrillogenesis was detected by Thioflavin T fluorometric assay. The levels of A beta(1-42) and inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Neuron viability was examined by the CCK-8 assay. The morphology of ZO-1 of bEnd.3 cultured in BV-2-conditioned medium was evaluated by immunofluorescence staining. Results: A beta fibrillogenesis was significantly inhibited by co-incubation with alpha-M, Zcbd-2 or Zcbd-3. alpha-M, Zcbd-2, Zcbd-3, and Zcbd-4 decreased the levels of A beta(1-42) and inflammatory cytokines, and promoted A beta uptake, degradation and anti-inflammation effects inflammation in microglia. alpha-M and Zcbd-3 protected neuron viability from A beta-induced neurotoxicity, and preserved tight junction integrity of bEnd.3 against LPS-induced neuroinflammation. Conclusion: Zcbd-3 acted as alpha-M almost in all effects. The structure-activity analysis indicated that the 3-methyl-2-butenyl group at C-8 is essential for the bioactivity of alpha-M, while modifying the double hydroxylation at the C-2 position may improve the multifunctional anti-AD effects.
关键词	alpha-mangostin Alzheimer's disease multifunctional structure-activity neuroinflammation amyloid beta BETA-AMYLOID PEPTIDES BLOOD-BRAIN-BARRIER CENTRAL-NERVOUS-SYSTEM ALPHA-MANGOSTIN MICROGLIA OLIGOMERS AGGREGATION MODULATION PRODUCTS DESIGN
DOI	10.3389/fchem.2022.842208
收录类别	SCI
WOS记录号	WOS:000804980400001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75657
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Hu, Xiaoyu,Liu, Chan,Wang, Kaichun,et al. Multifunctional Anti-Alzheimer's Disease Effects of Natural Xanthone Derivatives: A Primary Structure-Activity Evaluation[J]. FRONTIERS IN CHEMISTRY,2022,10:842208.
APA	Hu, Xiaoyu.,Liu, Chan.,Wang, Kaichun.,Zhao, Lanxue.,Qiu, Yu.,...&Xu, Jianrong.(2022).Multifunctional Anti-Alzheimer's Disease Effects of Natural Xanthone Derivatives: A Primary Structure-Activity Evaluation.FRONTIERS IN CHEMISTRY,10,842208.
MLA	Hu, Xiaoyu,et al."Multifunctional Anti-Alzheimer's Disease Effects of Natural Xanthone Derivatives: A Primary Structure-Activity Evaluation".FRONTIERS IN CHEMISTRY 10(2022):842208.

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