期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ijms22179583
关键词
amyloid-beta; Alzheimer's disease; luteolin; neurodegeneration; neuroprotection
资金
- Neurological Disorder Research Program of the National Research Foundation (NRF) - Korean Government (MSIT) [2020M3E5D9080660]
The study revealed that Luteolin has protective effects against amyloid-beta-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice, potentially through inhibition of JNK signaling and modulation of inflammatory and cell death markers.
The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (A beta(1)-(42))-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For the development of an AD mouse model, amyloid-beta (A beta(1)-(42), 5 mu L/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice's brain by using a stereotaxic frame. After that, the mice were treated with Luteolin for two weeks at a dose of 80 mg/kg/day. To monitor the biochemical changes, we conducted western blotting and immunofluorescence analysis. According to our findings, the infusion of amyloid-beta activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental mice; these changes were significantly inhibited in A beta(1)-(42) + Luteolin-treated mice. Likewise, we also checked the expression of inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB p65 (Ser536), tissue necrosis factor (TNF-alpha), and Interleukin1-beta (IL-1 beta), in A beta(1)-(42)-injected mice brain, which was attenuated in A beta(1)-(42) + Luteolin-treated mice brains. Further, we investigated the expression of pro- and anti-apoptotic cell death markers such as Bax, Bcl-2, Caspase-3, and Cox-2, which was significantly reduced in A beta(1)-(42) + Lut-treated mice brains compared to the brains of the A beta-injected group. The results also indicated that with the administration of A beta(1)-(42), the expression levels of beta-site amyloid precursor protein cleaving enzyme (BACE-1) and amyloid-beta (A beta(1)-(42)) were significantly enhanced, while they were reduced in A beta(1)-(42) + Luteolin-treated mice. We also checked the expression of synaptic markers such as PSD-95 and SNAP-25, which was significantly enhanced in A beta(1)-(42) + Lut-treated mice. To unveil the underlying factors responsible for the protective effects of Luteolin against AD, we used a specific JNK inhibitor, which suggested that Luteolin reduced A beta-associated neuroinflammation and neurodegeneration via inhibition of JNK. Collectively, our results indicate that Luteolin could serve as a novel therapeutic agent against AD-like pathological changes in mice.
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