Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized with a gradual loss of midbrain substantia nigra (SN) dopamine (DA) neurons. An excessive evidence demonstrated that microglia-mediated inflammation might be involved in the pathogenesis of PD. Thus, inhibition of neuroinflammation might possess a promising potential for PD treatment. Icariin (ICA), a single active component extracted from the Herba Epimedii, presents amounts of pharmacological properties, such as anti-inflammation, anti-oxidant, and anti-aging. Recent studies show ICA produced neuroprotection against brain dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are fully illuminated. In the present study, two different neurotoxins of 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS)-induced rat midbrain DA neuronal damage were applied to investigate the neuroprotective effects of ICA. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage and inhibited microglia activation and pro-inflammatory factors production via the suppression of nuclear factor-κB (NF-κB) pathway activation. In animal results, ICA significantly reduced microglia activation and significantly attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior changes. Together, ICA could protect DA neurons against LPS- and 6-OHDA-induced neurotoxicity both in vivo and in vitro. These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation.
Highlights
Parkinson’s disease (PD) is one of the most common neurodegenerative disease and characterized by the progressive loss of dopamine (DA) neurons in midbrain substantia nigra (SN) and the consequent movement malfunction (Towns, 2017)
Primary rat midbrain neuron-glia co-cultures were treated with ICA (0.01 and 0.1 μM) for 30 min followed by LPS (10 ng/ml) or 6-OHDA (40 μM) application
LPS/6-OHDA-elicited DA neuronal damage was quantified by DA neuronal counting via immunocytochemical staining and Tyrosine Hydroxylase (TH) protein expression through western blot assay
Summary
Parkinson’s disease (PD) is one of the most common neurodegenerative disease and characterized by the progressive loss of dopamine (DA) neurons in midbrain substantia nigra (SN) and the consequent movement malfunction (Towns, 2017). The resident immune cells in the central nervous system, present a series of changes in morphology and function after activated by an acute insult to the CNS (Gao et al, 2002; Gao and Hong, 2008). It was suggested that the damaged DA neurons and the activated microglia might create a vicious self-amplifying cycle eliciting the prolonged and uncontrolled inflammation that promotes the chronic progression of PD (Gao and Hong, 2008; Gao et al, 2011). Taken together, microgliamediated dynamic modulation of this neuroinflammation might be a key event in the degradation of DA neurons and inhibition of microglia-exerted vicious cycle could become a promising therapeutic potential for PD (Qian et al, 2010)
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