Di-caffeoylquinic acid: a potential inhibitor for amyloid-beta aggregation.

Autor: Sun Y; College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China.; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Wang X; Shandong Dongyue Polymer Materials Co., Ltd, Shandong, 256400, China., Zhang X; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China. zhangxiaoyu@dicp.ac.cn., Li Y; College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China.; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Wang D; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Sun F; College of Life Science, Liaoning Normal University, Dalian, 116081, China., Wang C; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Shi Z; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Yang X; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Yang Z; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Wei H; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China., Song Y; College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, China. yanlingsong521@126.com., Qing G; State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, National Chromatographic R. & A. Center, Chinese Academy of Sciences, Dalian, 116023, China. qinggy@dicp.ac.cn.
Jazyk: angličtina
Zdroj: Journal of natural medicines [J Nat Med] 2024 Sep; Vol. 78 (4), pp. 1029-1043. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1007/s11418-024-01825-y
Abstrakt: Alzheimer's disease (AD) remains a challenging neurodegenerative disorder with limited therapeutic success. Traditional Chinese Medicine (TCM), as a promising new source for AD, still requires further exploration to understand its complex components and mechanisms. Here, focused on addressing Aβ (1-40) aggregation, a hallmark of AD pathology, we employed a Thioflavin T fluorescence labeling method for screening the active molecular library of TCM which we established. Among the eight identified, 1,3-di-caffeoylquinic acid emerged as the most promising, exhibiting a robust binding affinity with a KD value of 26.7 nM. This study delves into the molecular intricacies by utilizing advanced techniques, including two-dimensional (2D) 15 N- 1 H heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and molecular docking simulations. These analyses revealed that 1,3-di-caffeoylquinic acid disrupts Aβ (1-40) self-aggregation by interacting with specific phenolic hydroxyl and amino acid residues, particularly at Met-35 in Aβ (1-40). Furthermore, at the cellular level, the identified compounds, especially 1,3-di-caffeoylquinic acid, demonstrated low toxicity and exhibited therapeutic potential by regulating mitochondrial membrane potential, reducing cell apoptosis, and mitigating Aβ (1-40)-induced cellular damage. This study presents a targeted exploration of catechol compounds with implications for effective interventions in AD and sheds light on the intricate molecular mechanisms underlying Aβ (1-40) aggregation disruption.
(© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)
Databáze: MEDLINE
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