2. Academic Validation
  3. Identification of ellagic acid and urolithins as natural inhibitors of Aβ25-35-induced neurotoxicity and the mechanism predication using network pharmacology analysis and molecular docking

Identification of ellagic acid and urolithins as natural inhibitors of Aβ25-35-induced neurotoxicity and the mechanism predication using network pharmacology analysis and molecular docking

  • Front Nutr. 2022 Aug 2:9:966276. doi: 10.3389/fnut.2022.966276.
Hui-Lin Li 1 2 3 4,  Shi-Ying Zhang 1 2 3,  Ying-Shan Ren 1 2 3,  Jie-Chun Zhou 1 2 3,  Ying-Xin Zhou 1 2 3,  Wei-Zhong Huang 5,  Xiu-Hong Piao 1 2 3 6,  Zhi-You Yang 7,  Shu-Mei Wang 1 2 3,  Yue-Wei Ge 1 2 3
Affiliations

Affiliations

  • 1 School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, China.
  • 2 Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou, China.
  • 3 Engineering and Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou, China.
  • 4 Macau University of Science and Technology, Macau, Macau SAR, China.
  • 5 Guangdong Luofushan Sinopharm Co., Ltd., Huizhou, China.
  • 6 School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
  • 7 Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China.
PMID: 35983489 DOI: 10.3389/fnut.2022.966276
Abstract

Ellagic acid (EA) is a dietary polyphenol that widely exists in grapes, strawberries, and walnuts. It usually exerts multiple biological activities together with its in vivo metabolites called urolithins. EA and urolithins had been proposed as natural agents for applying on the early intervention of Alzheimer's disease (AD). However, the neuroprotective effects of those small molecules have not been confirmed, and the action mechanism is not clear. Deposition of beta-amyloid (Aβ) protein is well documented as being involved in the initiation and pathological process of AD. In the present study, we investigated the attenuating effects of EA and several urolithins on Aβ25-35-induced neuronal injury and its underlying molecular mechanism by constructing the in vitro AD cell model of PC12 cells and primary neurons. The results revealed that EA and urolithins especially the UM5 and UM6 exerted promising neuroprotective effects in improving the Aβ25-35-induced cell damage and Lactate Dehydrogenase (LDH) leakage, reducing Reactive Oxygen Species (ROS) production, inhibiting neuronal Apoptosis, and promoting neurite outgrowth. These results provide new insights into the development of UM5 and UM6 as anti-AD candidates. A network pharmacology analysis combining molecular docking strategy was further adopted to predict the signaling pathway involved in the anti-AD action of EA and urolithins, and the activation of PI3K-Akt, as well as the inhibition of MAPK was found to be involved.

Keywords

Alzheimer’s disease; ellagic acid; natural inhibitor; neuroprotection; synaptic plasticity; urolithins.

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