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- Title
Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner.
- Authors
Zhang, Bei; Wang, Guoqing; He, Jingyi; Yang, Qiuyu; Li, Daidi; Li, Jingjie; Zhang, Feng
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Our findings identify that ICA attenuated glial cells-mediated neuroinflammation and evoked DA neuroprotection via an Nrf2-dependent manner.
- Subjects
DOPAMINE analysis; PARKINSON'S disease; KNOCKOUT mice; NEUROGLIA; CO-cultures; FACTORS of production; CELL metabolism; PROTEIN metabolism; ANIMALS; CELLS; DOPAMINE; FLAVONOIDS; INFLAMMATION; MICE; OXIDATIVE stress; NEUROPROTECTIVE agents; PARKINSONIAN disorders; PHARMACODYNAMICS
- Publication
Journal of Neuroinflammation, 2019, Vol 16, Issue 1, pN.PAG
- ISSN
1742-2094
- Publication type
journal article
- DOI
10.1186/s12974-019-1472-x