Objective: In this study, we examined neuroprotective effects of coffee ingredients, caffeic acid (CA) and chlorogenic acid (CGA), against rotenone-induced neurodegeneration using primary cultured cells and parkinsonian mice.

Background: Epidemiological analyses showed that daily drinking coffee and teas decreases the risk of Parkinson’s disease to 40-50%. Among coffee ingredients, CA has catechol structure and its ester with quinic acid, CGA exerts antioxidative properties. Rotenone as a pesticide, mitochondrial complex I inhibitor, has been used to reproduce neurodegeneration of enteric nervous system that precedes nigral dopaminergic neuronal loss.

Methods: Male C57BL/6J mice were chronically subcutaneously administered with low dose rotenone (2.5 mg/kg/day) for 4 weeks using an osmotic mini pump. The animals were daily orally treated with CA or CGA for 1 week before rotenone exposure and during 4-week rotenone infusion, totally for 5 weeks. Brain and intestinal sections were immunostained by antibodies for tyrosine hydroxylase (TH), β-tubulin III and GFAP. Primary cultured enteric neurons and glial cells were prepared from the intestine of Sprague-Dawley rat embryos at 15 days gestation. Cells were treated with CA or CGA for 24 h in advance, and then exposed to rotenone for 48 h.

Results: Chronic subcutaneous administration of rotenone reduced the number of TH-positive cells in the substantia nigra and immunoreactivities of β-tubulin III and GFAP in the intestinal myenteric plexus of mice. Daily administrations of CA or CGA inhibited rotenone-induced damage of not only nigral dopaminergic neurons but also enteric neurons and glial cells. In primary cultured cells, low dose rotenone promoted dose-dependent reduction of β-tubulin III-positive enteric neurons in the neuron-glia cocultured system but not in the enriched enteric neuronal culture. Furthermore, treatment with CA or CGA markedly prevented rotenone-induced cell loss of enteric neurons and astrocyte-like glial cells.

Conclusions: These results suggest that intake of coffee ingredients CA and CGA prevents rotenone-induced neurodegeneration in both of the brain and myenteric plexus.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotective-effects-of-coffee-ingredients-against-rotenone-induced-neurodegeneration-in-parkinsonian-model/