Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner.
In: Journal of neuroinflammation, Jg. 16 (2019-04-22), Heft 1, S. 92
Online
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Zugriff:
Background: Oxidative stress and neuroinflammation are considered the major central events in the process of Parkinson's disease (PD). Nrf2 is a key regulator of endogenous defense systems. New finds have contacted activation of Nrf2 signaling with anti-inflammatory activities. Therefore, the outstanding inhibition of neuroinflammation or potent Nrf2 signaling activation holds a promising strategy for PD treatment. Icariin (ICA), a natural compound derived from Herba Epimedii, presents a number of pharmacological properties, including anti-oxidation, anti-aging and anti-inflammatory actions. Recent studies have confirmed ICA exerted neuroprotection against neurodegenerative disorders. However, the underlying mechanisms were not fully elucidated.
Methods: In the present study, mouse nigral stereotaxic injection of 6-hydroxydopamine (6-OHDA)-induced PD model was performed to investigate ICA-conferred dopamine (DA) neuroprotection. In addition, adult Nrf2 knockout mice and primary rat midbrain neuron-glia co-culture was applied to elucidate whether ICA-exerted neuroprotection was through an Nrf2-dependent mechanism.
Results: Results indicated that ICA attenuated 6-OHDA-induced DA neurotoxicity and glial cells-mediated neuroinflammatory response. Furtherly, activation of Nrf2 signaling pathway in glial cells participated in ICA-produced neuroprotection, as revealed by the following observations. First, ICA enhanced Nrf2 signaling activation in 6-OHDA-induced mouse PD model. Second, ICA failed to generate DA neuroprotection and suppress glial cells-mediated pro-inflammatory factors production in Nrf2 knockout mice. Third, ICA exhibited neuroprotection in primary neuron-glia co-cultures but not in neuron-enriched cultures (without glial cells presence). Either, ICA-mediated neuroprotection was not discerned after Nrf2 siRNA treatment in neuron-glia co-cultures.
Conclusions: Our findings identify that ICA attenuated glial cells-mediated neuroinflammation and evoked DA neuroprotection via an Nrf2-dependent manner.
Titel: |
Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner.
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Autor/in / Beteiligte Person: | Zhang, B ; Wang, G ; He, J ; Yang, Q ; Li, D ; Li, J ; Zhang, F |
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Zeitschrift: | Journal of neuroinflammation, Jg. 16 (2019-04-22), Heft 1, S. 92 |
Veröffentlichung: | [London] : BioMed Central, c2004-, 2019 |
Medientyp: | academicJournal |
ISSN: | 1742-2094 (electronic) |
DOI: | 10.1186/s12974-019-1472-x |
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