Luteolin inhibits SH-SY5Y cell apoptosis through suppression of the nuclear transcription factor-κB, mitogen‑activated protein kinase and protein kinase B pathways in lipopolysaccharide-stimulated cocultured BV2 cells

Zhu,Lihong; Bi,Wei; Lu,Dan; Zhang,Chanjuan; Shu,Xiaoming; Lu,Daxiang

doi:10.3892/etm.2014.1564

Luteolin inhibits SH-SY5Y cell apoptosis through suppression of the nuclear transcription factor-κB, mitogen‑activated protein kinase and protein kinase B pathways in lipopolysaccharide-stimulated cocultured BV2 cells

Authors:
- Lihong Zhu
- Wei Bi
- Dan Lu
- Chanjuan Zhang
- Xiaoming Shu
- Daxiang Lu
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Affiliations: Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China
Published online on: February 20, 2014 https://doi.org/10.3892/etm.2014.1564
Pages: 1065-1070

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Abstract

Microglial activation is one of the causative factors for neuroinflammation, which is associated with the pathophysiology of neurodegenerative diseases. Our previous study showed that the flavonoid luteolin inhibited several pro-inflammatory enzymes and pro-inflammatory cytokines that are induced by activated microglia; however, its effect on signaling pathways is currently unknown. The present study examined the effects of luteolin on signaling pathways stimulated by lipopolysaccharide (LPS), including Toll-like receptor-4 (TLR-4), nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) family and protein kinase B (Akt) pathways in murine microglial BV2 cells. In addition, BV2 microglia and SH-SY5Y neuroblastoma cells were cocultured to observe the indirect neuroprotective effects of luteolin. Luteolin inhibited the LPS-stimulated expression of TLR-4. In addition, luteolin blocked LPS-induced NF-κB, p38, JNK and Akt activation, but had no effect on ERK. When SH-SY5Y cells were cocultured with LPS-stimulated BV2 microglia, pretreatment with luteolin increased neuronal viability and reduced the number of apoptotic cells. These data suggest that luteolin has a beneficial effect on neuroinflammatory events in neurodegenerative diseases via suppression of the NF-κB, MAPK and Akt pathways in activated microglial cells.

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