Grape seed proanthocyanidin extract chelates iron and attenuates the toxic effects of 6-hydroxydopamine: Implications for Parkinson's disease

Proanthocyanidins are potent antioxidants associated with protection against diseases. We tested the reducing capacity, iron chelating activity, and anti-auto-oxidation ability of grape seed proanthocyanidin extract (GSPE). The mechanisms underlying GSPE attenuation of oxidative processes induced by 6-hydroxydopamine (6-OHDA), a neurotoxin used to induce Parkinson's disease, were investigated in cell-based systems. At high concentrations, GSPE (50 μg/μL) was a mild pro-oxidant in a Fenton-type reaction. GSPE (300 μg/mL) was as potent as 30 μM deferoxamine in its iron-chelating capacity, and as efficient as 5 mM ascorbic acid in delaying 6-OHDA auto-oxidation. In PC-12 cell cultures, 100 and 300 μg/mL GSPE significantly protected (P <0.05) cells from 6-OHDA-induced (400 μM) toxicity. GSPE-induced cytoprotection is enhanced by a nitric oxide synthase inhibitor (NOSI), implying that the cytoprotective effect of GSPE does not require NOS activation. In conclusion, the iron-chelating activity of GSPE minimizes its pro-oxidant activity and delays 6-OHDA auto-oxidation to provide cytoprotection.