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Planta Med 2023; 89(10): 990-1000
DOI: 10.1055/a-2014-6061
Biological and Pharmacological Activity
Original Papers

Network Pharmacology and Mechanism Studies of the Protective Effect of Ginseng against Alzheimerʼs Disease Based on Aβ Pathogenesis

Jinman Liu 
1   Affiliated Jiangmen TCM Hospital of Jiʼnan University, Jiangmen, China
,
Wenqian Yu
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Cuiru Ma
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Tianyao Li
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Yong Liang
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Shijie Su
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Guangcheng Zhong
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Zhouyuan Xie
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Qiqing Wu
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Jiaxin Chen
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
,
Qi Wang
2   Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
› Author AffiliationsSupported by: Key laboratory project of colleges and universities in Guangdong province 2019KSYS005
Supported by: science and technology program of Guangzhou 202201011195
Supported by: National Natural Science Foundation of China 21904110
Supported by: National Natural Science Foundation of China 81973918
Supported by: Guangdong province science and technology plan international cooperation project 2020A0505100052
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Abstract

Alzheimerʼs disease (AD) is a critical neurodegenerative disease that manifests as progressive intellectual decline and is pathologically characterized by a progressive loss of neurons in the brain. Despite extensive research on this topic, the pathogenesis of AD is not fully understood, while the beta-amyloid (Aβ) hypothesis remains the dominant one and only a few symptomatic drugs are approved for the treatment of AD. Ginseng has been widely reported as an effective herbal medicine for the treatment of neurodegenerative diseases such as dementia. Therefore, we explore the protective effects of ginseng in AD by a network pharmacological approach based on the pathogenesis of Aβ. Twenty-one major ginsenosides are screened based on ultraperformance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) data. Among them, MAPK8, MAPK9, BACE1, FLT1, CDK2, and CCR5 are the core targets. By molecular docking and validation with the in vitro cell model APPswe-SH-SY5Y, we find that ginsenosides Rg3 and Ro have good neuroprotective effects and can reduce the expression of Aβ 1 – 42 in APPswe-SH-SY5Y. Finally, through RT-qPCR experiment, we find that ginsenoside Rg3 targeted MAPK8, FLT1, and CCR5, while ginsenoside Ro targeted MAPK8, MAPK9, FLT1, and CCR5 for its potential anti-AD efficacy.

Key words

Ginseng - Araliaceae - Alzheimerʼs disease - beta-amyloid - network pharmacology - targets

Supporting Information

    Schematic diagram of molecular docking results of donepezil, dose-dependent experiments for copper to cause APPswe-SH-SY5Y cell injury and apoptosis model, the mean contents of ginsenosides and their standard deviation and standard error, major ginsenosides in ginseng and their properties, ranking of 60 genes targeting Aβ in ginsenosides by degree, enrichment analysis in DisGeNET, and primers used for real-time quantitative PCR are available as supporting information.

  • Supporting Information


Publication History

Received: 15 October 2022

Accepted after revision: 16 January 2023

Accepted Manuscript online:
17 January 2023

Article published online:
14 July 2023

© 2023. Thieme. All rights reserved.

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