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Anti-inflammatory activity of hydroxytyrosol – Inhibition of cytokine production in a parkinson’s model system of neuroinflammation

corresponding

ROBERTO CREA1*, CATHERINE M. BITLER1, LAUREL M. BOLIN2, PAOLO PONTONIERE1

Corresponding author

1. CreAgri, Inc., 25565 Whitesell Street, Hayward, CA 94545, USA

2. The Parkinson’s Institute, Sunnyvale, CA 94085, USA

Abstract

The Mediterranean diet, consisting of high concentrations of natural polyphenols and flavonoids, is associated with a low incidence of cancer, diabetes and cardiovascular disease. Olive phenolics, in particular hydroxytyrosol, demonstrate some of the highest free-radical scavenging and anti-inflammatory activities of known naturally-occurring antioxidants. Here we demonstrate that hydrolyzed olive vegetation water (Liquid Hidrox® or Hidrox®), a proprietary formulation of olive polyphenols rich in hydroxytyrosol, inhibits the production of pro-inflammatory cytokines in an in vitro model of neuroinflammation. In contrast oleuropein, the principal phenolic in olive leaf, was significantly less effective at inhibiting cytokine production. These results suggest that the anti-inflammatory activity of hydroxytyrosol may impact neuroinflammation in Parkinson’s and other neurodegenerative diseases.


INTRODUCTION

Parkinson's disease is a progressive neurodegenerative disorder that clinically presents itself with motor neuron deficits that include shuffling gait, rigidity, and tremor (1). The pathological component of Parkinson's disease is a degeneration of neurons that project from the substantia nigra to the striatum, resulting in a reduction in striatal dopamine. Motor loss is proportional to the resultant dopamine deficiency associated with the disease (2).
In addition to understanding the neuronal cell loss, there is mounting interest in the role of neuroinflammation in Parkinson's disease. Neuroinflammation, resulting from uncontrolled microglial activation, appears to contribute to the neuronal damage seen in Parkinson’s disease. The discovery of major histocompatibility complex-positive reactive microglia in the parkinsonian substantia nigra (3), and the detection of elevated cytokines in the spinal fluid of Parkinson's disease patients (4) and in the substantia nigra of post-mortem parkinsonian brains (5) strongly indicate that inflammation plays a key role in the pathology of Parkinson's disease (6).
Reactive microglia cel ...