Ginsenoside Rg_1 protects PC12 cells against Aβ-induced injury through promotion of mitophagy by PINK1/parkin activation.
10.19540/j.cnki.cjcmm.20210901.703
- Author:
He-Mei LI
1
;
Yi-Xuan JIANG
1
;
Pan-Ling HUANG
1
;
Bo-Cun LI
1
;
Zi-Yu PAN
1
;
Yu-Qing LI
2
;
Xing XIA
3
Author Information
1. College of Pharmacy, Guangxi University of Chinese Medicine Nanning 530200, China.
2. College of Public Health and Management, Guangxi University of Chinese Medicine Nanning 530200, China.
3. College of Pharmacy, Guangxi University of Chinese Medicine Nanning 530200, China The Key Laboratory of Chinese Medicine Pharmacology of Colleges and Universities in Guangxi, Guangxi University of Chinese Medicine Nanning 530200, China.
- Publication Type:Journal Article
- Keywords:
PINK1;
amyloid β-protein;
ginsenoside Rg_1;
mitophagy
- MeSH:
Amyloid beta-Peptides/toxicity*;
Animals;
Ginsenosides/pharmacology*;
Humans;
Mitophagy/physiology*;
PC12 Cells;
Protein Kinases/metabolism*;
Rats;
Ubiquitin-Protein Ligases/metabolism*
- From:
China Journal of Chinese Materia Medica
2022;47(2):484-491
- CountryChina
- Language:Chinese
-
Abstract:
Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.
