Effect of Bushen Huoxue Granule on Clearance of Pathological α-Synuclein in MPP+-Induced PC12 Cells.
10.1007/s11655-025-3707-2
- Author:
Zhen-Xian LUAN
1
;
Xiang-Lin TANG
1
;
Fei-Ran HAO
1
;
Min LI
1
;
Shao-Dan LI
1
;
Ming-Hui YANG
2
Author Information
1. Medical Department of Traditional Chinese Medicine, the Sixth Medical Center of the PLA General Hospital, Beijing, 100048, China.
2. Medical Department of Traditional Chinese Medicine, the Sixth Medical Center of the PLA General Hospital, Beijing, 100048, China. Ymh9651@sina.com.
- Publication Type:Journal Article
- Keywords:
1-methyl-4-phenylpyridinium;
Bushen Huoxue Granule;
Chinese medicine;
Parkinson’s disease;
ubiquitin-proteasome system;
α-synuclein
- MeSH:
PC12 Cells;
alpha-Synuclein/metabolism*;
Rats;
Animals;
1-Methyl-4-phenylpyridinium/toxicity*;
Proteasome Endopeptidase Complex/metabolism*;
Drugs, Chinese Herbal/pharmacology*;
Ubiquitin/metabolism*;
Cell Survival/drug effects*;
Phosphorylation/drug effects*;
Tyrosine 3-Monooxygenase/metabolism*
- From:
Chinese journal of integrative medicine
2025;31(9):830-836
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease.
METHODS:After treated with 1-methyl-4-phenylpyridinium (MPP+, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay.
RESULTS:BCS (volume fraction ⩽20%) intervention could alleviate the MMP+-induced cell viability decrease (P<0.05). In the MPP+ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP+-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP+-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05).
CONCLUSION:BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP+ in the in vitro model of Parkinson's disease.
