Thonningianin A from Penthorum chinense Pursh as a targeted inhibitor of Alzheimer's disease-related β-amyloid and Tau proteins

被引：3

作者：

Yu, Lu ^{[1
,2
,3
]}

Wang, Huimiao ^{[2
]}

Yao, Qianfang ^{[1
]}

Li, Keru ^{[1
]}

Qu, Liqun ^{[2
]}

Tang, Bin ^{[2
]}

Zeng, Wu ^{[2
]}

Qiao, Gan ^{[4
]}

Tang, Yong ^{[1
,2
]}

Hu, Guishan ^{[1
]}

Hu, Guangqiang ^{[1
]}

Wong, Vincent Kam-Wai ^{[2
]}

Wang, Qiong ^{[5
]}

Qin, Dalian ^{[1
]}

Wu, Jianming ^{[1
]}

Zhou, Xiaogang ^{[1
]}

Sun, Xiaolei ^{[6
]}

Law, Betty Yuen-Kwan ^{[2
]}

Wu, Anguo ^{[1
]}

机构：

[1] Southwest Med Univ, Minist Educ,Key Lab Med Electrophysiol, Sichuan Key Med Lab New Drug Discovery & Drugabil, Luzhou Key Lab Act Screening & Druggabil Evaluat,S, Luzhou 646000, Peoples R China

[2] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China

[3] Southwest Med Univ, Sch Preclin Med, Dept Chem, Luzhou, Peoples R China

[4] Southwest Med Univ, Nucl Acid Med Luzhou Key Lab, Cent Nervous Syst Drug Key Lab Sichuan Prov, Luzhou, Peoples R China

[5] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Sino Portugal TCM Int Cooperat Ctr, Luzhou, Peoples R China

[6] Southwest Med Univ, Dept Vasc Surg, Affiliated Hosp, Luzhou, Peoples R China

来源：

PHYTOTHERAPY RESEARCH | 2024年 / 38卷 / 09期

基金：

中国国家自然科学基金;

关键词：

3xTg-AD mice; Alzheimer's disease; A beta; mitochondrial damage; Penthorum chinense Pursh; reactive oxygen species; Tau; thonningianin A; NLRP3; INFLAMMASOME; HYPERPHOSPHORYLATION; PHOSPHORYLATION; POLYPHENOLS;

D O I：

10.1002/ptr.8060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, beta-amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression. The inhibitory potential of PCP and TA on A beta fibrillization was initially investigated. Subsequently, ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and biolayer interferometry were employed to determine TA's affinity for both A beta and Tau. The inhibitory effects of TA on the levels and cytotoxicity of AD-related proteins were then assessed. In 3xTg-AD mice, the therapeutic potential of TA was evaluated. Additionally, the molecular interactions between TA and either A beta or Tau were explored using molecular docking. We found that PCP-total ethanol extract and TA significantly inhibited A beta fibrillization. Additionally, TA demonstrated strong affinity to A beta and Tau, reduced levels of amyloid precursor protein and Tau, and alleviated mitochondrial distress in PC-12 cells. In 3xTg-AD mice, TA improved cognition, reduced A beta and Tau pathology, and strengthened neurons. Moreover, molecular analyses revealed efficient binding of TA to A beta and Tau. In conclusion, TA, derived from PCP, shows significant neuroprotection against AD proteins, highlighting its potential as an anti-AD drug candidate.

引用

页码：4815 / 4831

页数：17

共 41 条

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