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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia
Mei-Jen Wang1, Wan-Wan Lin, Huan-Lian Chen
1Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
Abstract:
An inflammatory response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Silymarin is a polyphenolic flavanoid derived from milk thistle that has anti-inflammatory, cytoprotective and anticarcinogenic effects. In this study, we first investigated the neuroprotective effect of silymarin against lipopolysaccharide (LPS)-induced neurotoxicity in mesencephalic mixed neuron-glia cultures. The results showed that silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons. Therefore, the inhibitory mechanisms of silymarin on microglia activation were studied further. The production of inducible nitric oxide synthase (iNOS) was studied in LPS-stimulated BV-2 cells as a model of microglia activation. Silymarin significantly reduced the LPS-induced nitrite, iNOS mRNA and protein levels in a dose-dependent manner. Moreover, LPS could induce the activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase but not extracellular signal-regulated kinase. The LPS-induced production of NO was inhibited by the selective p38 MAPK inhibitor SB203580. These results indicated that the p38 MAPK signalling pathway was involved in the LPS-induced NO production. However, the activation of p38 MAPK was not inhibited by silymarin. Nevertheless, silymarin could effectively reduce LPS-induced superoxide generation and nuclear factor kappaB (NF-kappaB) activation. It suggests that the inhibitory effect of silymarin on microglia activation is mediated through the inhibition of NF-kappaB activation.
Insights
Silymarin, derived from milk thistle, protects brain cells by reducing inflammation and damage in neurodegenerative diseases. It inhibits microglial activation by suppressing nuclear factor-kappaB (NF-kappaB) signaling.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Neuroinflammation, driven by microglia activation, is crucial in neurodegenerative diseases.
- Silymarin, a milk thistle flavonoid, exhibits anti-inflammatory and cytoprotective properties.
Purpose of the Study:
- To investigate the neuroprotective effects of silymarin against lipopolysaccharide (LPS)-induced neurotoxicity.
- To elucidate the mechanisms underlying silymarin's inhibition of microglia activation.
Main Methods:
- Primary mesencephalic neuron-glia cultures and BV-2 microglia cell line.
- Assessment of microglia activation, inflammatory mediator production (TNF-α, NO), dopaminergic neuron damage, iNOS expression, MAPK signaling, superoxide generation, and NF-kappaB activation.
Main Results:
- Silymarin reduced LPS-induced microglia activation, inflammatory mediators, and dopaminergic neuron damage.
- Silymarin dose-dependently inhibited nitrite and iNOS production.
- Silymarin suppressed LPS-induced superoxide generation and NF-kappaB activation, but not p38 MAPK activation.
Conclusions:
- Silymarin demonstrates neuroprotective effects against LPS-induced neurotoxicity.
- Silymarin's mechanism involves inhibiting microglial activation via the NF-kappaB pathway.