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Ginsenoside Rg1 ameliorates Alzheimer's disease pathology via restoring mitophagy
Ni Wang2022
Yang JunyanRuijun Chen
Top 15% · 85th percentile
66 citations · Molecular Biology
Open Access

TLDR

A natural compound from ginseng called Rg1 helps protect the brain in Alzheimer's disease by cleaning up damaged parts of cells and improving memory in mice.

Summary

1 Study Aim

The main goal of this study is to find out if ginsenoside Rg1, a compound from ginseng, can reduce the harmful effects of Alzheimer's disease by fixing problems with mitophagy (the process that removes damaged mitochondria, which are the cell's energy producers). The researchers want to see if Rg1 can protect brain cells and improve memory by restoring this cleaning process in both cell and mouse models of Alzheimer's disease. Simply put: The study wants to see if a ginseng compound can help the brain by cleaning up damaged cell parts in Alzheimer's.

2 Study Design

The researchers used human SH-SY5Y nerve cells and a special mouse model called 5XFAD, which develops Alzheimer's-like symptoms. In the cell experiments, they added a toxic protein (AβO) or a mutated gene (APPswe) to mimic Alzheimer's, then treated the cells with Rg1 for 24 hours. In the mouse experiments, they injected Rg1 daily for 30 days. They measured markers of mitophagy using lab techniques like western blot and immunofluorescence, checked memory with the Morris water maze, and looked at brain tissue under an electron microscope. They also tested if Rg1 activated the PINK1/Parkin pathway (a key mitophagy process). Simply put: The study tested a ginseng compound in brain cells and mice with Alzheimer's symptoms to see if it helps clean up cell damage and improve memory.

3 Findings

The study reveals that Rg1 treatment restores mitophagy in both Alzheimer's cell and mouse models, mainly by activating the PINK1/Parkin pathway (a system that helps remove damaged mitochondria). In mice, Rg1 improved memory performance and reduced cell death in the brain. The researchers also found that Rg1 lowered the amount and size of harmful protein deposits (β-amyloid) in the brain, possibly by helping immune cells called microglia clear them away. No harmful effects were seen in the liver or kidneys. The authors suggest that Rg1 could be a promising treatment for Alzheimer's disease by supporting the brain's natural cleaning systems. Simply put: The study found that a ginseng compound helps the brain get rid of damaged parts, improves memory, and reduces harmful buildup in Alzheimer's mice.

Abstract

Background: Alzheimer's disease (AD) is a common form of dementia, and impaired mitophagy is a hallmark of AD. Mitophagy is mitochondrial-specific autophagy. Ginsenosides from Ginseng involve in autophagy in cancer. Ginsenoside Rg1 (Rg1 hereafter), a single compound of Ginseng, has neuroprotective effects on AD. However, few studies have reported whether Rg1 can ameliorate AD pathology by regulating mitophagy. Methods: Human SH-SY5Y cell and a 5XFAD mouse model were used to investigate the effects of Rg1. Rg1 (1μM) was added to β-amyloid oligomer (AβO)-induced or APPswe-overexpressed cell models for 24 hours. 5XFAD mouse models were intraperitoneally injected with Rg1 (10 mg/kg/d) for 30 days. Expression levels of mitophagy-related markers were analyzed by western blot and immunofluorescent staining. Cognitive function was assessed by Morris water maze. Mitophagic events were observed using transmission electron microscopy, western blot, and immunofluorescent staining from mouse hippocampus. The activation of the PINK1/Parkin pathway was examined using an immunoprecipitation assay. Results: Rg1 could restore mitophagy and ameliorate memory deficits in the AD cellular and/or mouse model through the PINK1-Parkin pathway. Moreover, Rg1 might induce microglial phagocytosis to reduce β-amyloid (Aβ) deposits in the hippocampus of AD mice. Conclusion: Our studies demonstrate the neuroprotective mechanism of ginsenoside Rg1 in AD models. Rg1 induces PINK-Parkin mediated mitophagy and ameliorates memory deficits in 5XFAD mouse models.

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