Effects of bromelain on striatal neuroinflammation in rat model of Parkinsonism

Abstract

Background: Neuroinflammation alters the microenvironment in certain areas of the brain resulting in the development of Parkinson's disease (PD). Mechanisms involving cytokine and non-cytokine induced pathways are activated in the inflammatory response following injury. The proteolytic activity of bromelain appears to eliminate receptors on immune cells that respond to pro-inflammatory signals. This raises the question of whether manipulation of the inflammatory response pathways could lead to a beneficial intervention for PD. In this study, we investigated the effect of bromelain exposure on pro-inflammatory cytokine concentration and microglial activation in a parkinsonian rat model. Methods: Nigrostriatal dopamine neurons were lesioned by stereotaxic injection of the neurotoxin, 6-OHDA, into the medial forebrain bundle (MFB) of male Sprague-Dawley rats with weight ranging from 230- 250 g. The anti-inflammatory drug bromelain was used to treat a subset of the rats before or 24 h post 6-OHDA lesion. The systemic blood concentration of neutrophils and platelets was measured along with plasma and striatal concentrations of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. In addition, the densities of CD11b and CD86 cells were differently quantified as a measure of glial cell activation. ResultsPre-treatment with bromelain decreased the plasma concentration of neutrophils and platelets in 6-OHDA lesioned rats. The bromelain treatments (Pre and Post) decreased the plasma concentration of TNF-α and IL-1β. Pre-treatment with bromelain further resulted in the suppression of both systemic pro-inflammatory cytokines and microgliosis. Post-surgical bromelain treatment significantly resulted in the alleviation of systemic pro-inflammatory cytokines. ConclusionEarly treatment with bromelain may slow the progression of PD by attenuating the inflammatory response associated with the disease. The present results suggest that bromelain may be considered for further clinical study and perhaps use as prophylactic treatment for patients with PD.