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
