Protective effect of hydroxysafflor yellow A on dopaminergic neurons against 6-hydroxydopamine, activating anti-apoptotic and anti-neuroinflammatory pathways.
CONTEXT
Hydroxysafflor yellow A (HSYA) has been shown to have neuroprotective effects in cerebral infarction. However, its underlying roles in apoptosis and inflammation in Parkinson's disease (PD) are unknown.


OBJECTIVE
The present study investigates the effects and underlying mechanisms of HSYA on dopaminergic (DA) neurodegeneration, inflammation, and apoptosis.


MATERIALS AND METHODS
The PD model was established by 2 μL of 6-hyroxydopamine (6-OHDA) (3 μg/μL) striatal injection in C57BL/6J mice with different doses of HSYA (2, 4, or 8 mg/kg). In vitro, after being treated with HSYA for 1 h, SH-SY5Y cells were exposed to 6-OHDA for 24 h before analysis. Expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and corpus striatum (STR) was evaluated by immunohistochemistry (IHC) and western blot. In addition, apoptosis-related and inflammatory proteins were examined by western blot.


RESULTS
Administration of HSYA significantly reduced the Apomorphine (APO)-induced rotation, decreased from 122.5 ± 15.1 (6-OHDA group) to 47.2 ± 14.3 (8 mg/kg HSYA group). HSYA partially restored a deficit in the SN and STR of PD mice brains in TH. Furthermore, western blot analysis revealed that HSYA reduced inflammatory proteins, including iNOS, COX-2 and NF-κB and attenuated the elevation of DA neuronal apoptosis observed in PD. In vitro assays showed that HSYA reduced the levels of p-p38 and p-JNK and increased that of p-ERK in 6-OHDA-leisoned SH-SY5Y cells.


CONCLUSIONS
These findings indicate that HSYA protects against 6-OHDA induced DA neurodegeneration partly by regulating the MAPK inflammatory signalling pathway and apoptosis which highlight its therapeutic potential in the treatment of PD.
['Yang|Xiaomei|X|', 'Li|Yun|Y|', 'Chen|Lin|L|', 'Xu|Mingguo|M|', 'Wu|Jianbo|J|', 'Zhang|Peng|P|', 'Nel|Deon|D|', 'Sun|Baozhu|B|']
D000818:Animals D017209:Apoptosis D002599:Chalcone D003342:Corpus Striatum D004298:Dopamine D059290:Dopaminergic Neurons D004305:Dose-Response Relationship, Drug D007249:Inflammation D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018696:Neuroprotective Agents D016627:Oxidopamine D020734:Parkinsonian Disorders D011809:Quinones D015398:Signal Transduction
apoptosis Parkinson’s disease p38 MAPK pathway