Abstract
Parkinson’s disease (PD) is caused by the loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation, which is marked by microglial activation, plays a very important role in the pathogenesis of PD. Pro-inflammatory mediators produced by activated microglia could damage DA neurons. Hence, the inhibition of microglial activation may provide a new approach for treating PD. Galangin has been shown to inhibit inflammation in a variety of diseases, but not PD. In this study, we aimed to investigate the anti-inflammatory effect of galangin and the underlying mechanisms in Lipopolysaccharide (LPS) induced PD models. We first examined the protective effect of galangin in the LPS-induced PD rat model. Specifically, we investigated the effects on motor dysfunction, microglial activation, and the loss of DA neurons. Then, galangin was used to detect the impact on the inflammatory responses and inflammatory signaling pathways in LPS-induced BV-2 cells. The in vivo results showed that galangin dose-dependently attenuates the activation of microglia, the loss of DA neurons, and motor dysfunction. In vitro, galangin markedly inhibited LPS-induced expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase 2 (COX-2), and induced nitric oxide synthase (iNOS) via associating with the phosphorylation of c-JUN N-terminal Kinase (JNK), p38, protein kinase B (AKT), and nuclear factor κB (NF-κB) p65. Collectively, the results indicated that galangin has a role in protecting DA neurons by inhibiting microglial activation.
Highlights
Parkinson’s disease (PD) is one of the common neurodegenerative disorders and affects over 4 million people worldwide [1]
The characteristic feature of PD is the loss of DA neurons in the midbrain substantia nigra (SN), which leads to bradykinesia, postural instability, resting tremor, and rigidity of patients [2,3,4]
PPrreevviioouuss ssttuuddiieess hhaavvee shown that galangin has anti-inflflammatory functions in various diseases
Summary
Parkinson’s disease (PD) is one of the common neurodegenerative disorders and affects over 4 million people worldwide [1]. The characteristic feature of PD is the loss of DA neurons in the midbrain substantia nigra (SN), which leads to bradykinesia, postural instability, resting tremor, and rigidity of patients [2,3,4]. Existing treatments provide benefits for PD patients, medications to cure or slow the progress of PD are still poor. Neuroinflammation was reported to be an important mechanism responsible for the pathogenesis of PD [5,6]. Normal neuroinflammation is important to protect the central nervous system (CNS). Uncontrolled and prolonged neuroinflammation is potentially harmful and can cause damage of DA neurons [7]. The mark of neuroinflammation is the activation of microglia. Pro-inflammatory mediators, produced by activated microglia, are responsible for the damage to DA neurons. Inhibition of over-activation of microglia may provide a new approach for treating PD
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