Background
Parkinson's disease (PD) is a common neurodegenerative disorder. Cinnamon procyanidin oligomers (CPOs) are flavonoids with many claimed health benefits.
Conclusion
CPO-A protected against MPP+-induced cytotoxicity in SH-SY5Y cells and MPTP-induced neurotoxicity in mice by regulating the P38MAPK/P53/BAX signaling. Our findings reveal a novel role and mechanism of a food flavonoid CPO-A in preventing neurodegeneration.
Methods
Thirty male mice (C57BL/6, 9-wk old) were assigned to 3 groups (n = 10), and were given daily gavage of saline [control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) groups] or CPO-A (150 mg/kg, CPO-A group) during days 1-15 and daily intraperitoneal injections of saline (control group) or MPTP (20 mg/kg; MPTP and MPTP + CPO-A groups) during days 11-15. After the motor behavior test, all mice were killed on day 16 to collect the substantia nigra (SN) for assaying the neuroprotective effects of CPO-A. SH-SY5Y cells were treated with 12.5 μM CPO-A for 2 h or 3 activators of stress-related kinases (5-25 μM) for 12-48 h followed by 1 mM 1-methyl-4-phenylpyridinium (MPP+) for assays of viability, morphology, and stress status.
Objective
This study aimed to elucidate the neuroprotection of A-type CPOs (CPO-A) and the underlying mechanisms in cultured cell and animal models of PD.
Results
Compared with the control, the MPTP treatment decreased (P < 0.05) locomotor activity by 21%, and tyrosine hydroxylase (TH) positive neurons by 55% and Th mRNA concentration by 51% in the SN. The CPO-A treatment attenuated or restored (P < 0.05) these changes and inhibited (P < 0.05) the MPTP-induced activation of P38 mitogen-activated protein kinase (P38MAPK) and P53, along with the downstream expression of BCL-2 associated X protein (BAX) in the SN. In SH-SY5Y cells, the CPO-A treatment blocked (P < 0.01) the MPP+-induced accumulation of intracellular reactive oxygen species and neurotoxicity. However, this protection was abolished (P < 0.05) by activators of the P38MAPK/P53/BAX pathway.