Phenolamides from Rootstocks of Lycium ruthenicum Murr by Ligand Fishing and Their Neuroprotective Effects

被引：0
作者：
Hu, Yi-Kao [1 ]
Ablat, Ayzohra [1 ,2 ]
Bai, Xiao-Lin [1 ,2 ]
Yin, Xiang [1 ,2 ]
Ma, Chao [3 ]
Liao, Xun [1 ]
机构：
[1] Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Tibet Plateau Inst Biol, Phytochem Lab, Lhasa 850001, Peoples R China
来源：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2025年
基金：
中国国家自然科学基金;
关键词：
Lycium ruthenicum Murr; rootstocks; phenolamides; neuroprotective effect; mechanism; ligand fishing; OXIDATIVE STRESS; INHIBITION; KUKOAMINE;
D O I：
10.1021/acs.jafc.4c11099
中图分类号：
S [农业科学];
学科分类号：
09 ;
摘要：
Lycium ruthenicum Murr is an important edible and medicinal plant widely cultivated in Northwest China. Our previous study found that its fruit possessed rich polyphenols exhibiting significant neuroprotective effects, inspiring us to investigate the active constituents of its rootstocks, which have never been reported. In this study, we rapidly identified four phenolamides (1-4) possessing monoamine oxidase B (MAO-B) inhibitory effect by using MAO-B-functionalized cellulose filter paper-based ligand fishing, and their structures were elucidated with NMR and MS. Compounds 1, 2, and 4 exhibited moderate inhibitory effect on MAO-B with IC50 values of 71.44 +/- 1.81, 28.97 +/- 1.20, and 25.58 +/- 0.74 mu M, respectively, and enzyme kinetic analysis, molecular docking, and molecular dynamics further revealed the inhibition mechanism. All four phenolamides displayed a neuroprotective effect against 1-methyl-4-phenylpyridinium -induced SH-SY5Y cells model, among which 2 and 4 significantly reduced intracellular MAO-B activity and improved the ATP content. Western blot revealed that compounds 2 and 4 alleviated the oxidative stress through up-regulation of the expression of Nrf2 and HO-1 protein, promoting mitophagy via activating the PINK1/Parkin pathway. Moreover, compounds 2 and 4 extended the lifespan, dopamine and ATP levels, locomotor behavior, and olfactory ability of the PINK1 B9 flies, a drosophila model of Parkinson's disease. Meanwhile, compounds 1-4 showed potent antioxidative activities on DPPH, ABTS+, and PTIO radical scavenging assays. These results revealed the health-promoting effects of the rootstocks in preventing and treating neurodegenerative diseases, laying the scientific foundation for the exploitation of this plant byproduct for the development of functional food formulations and pharmaceutical products.
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页码：8944 / 8958
页数：15
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