title: 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.
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.
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Shu
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Lu
keywords: Toll-like receptor 4; luteolin; microglia; mitogen-activated protein kinase; neuroinflammation; neuroprotection; nuclear transcription factor κB; protein kinase B