Luteolin Mitigates Dopaminergic Neuron Degeneration and Restrains Microglial M1 Polarization by Inhibiting Toll Like Receptor 4

木犀草素 神经炎症 神经保护 小胶质细胞 神经退行性变 TLR4型 化学 多巴胺能 药理学 细胞生物学 受体 生物 炎症 免疫学 生物化学 神经科学 多巴胺 医学 内科学 类黄酮 抗氧化剂 疾病
作者
Yangzhi Xie,Hao Zhang,Jiacheng Chen,Shikun Xu,Yan Luo
出处
期刊:Journal of Integrative Neuroscience [IMR Press]
卷期号:23 (10)
标识
DOI:10.31083/j.jin2310185
摘要

Background: Luteolin is a natural flavonoid and its neuroprotective and anti-inflammatory effects have been confirmed to mitigate neurodegeneration. Despite these findings, the underlying mechanisms responsible for these effects remain unclear. Toll-like receptor 4 (TLR4) is widely distributed in microglia and plays a pivotal role in neuroinflammation and neurodegeneration. Here studies are outlined that aimed at determining the mechanisms responsible for the anti-inflammatory and neuroprotective actions of luteolin using a rodent model of Parkinson's disease (PD) and specifically focusing on the role of TLR4 in this process. Methods: The mouse model of PD used in this experiment was established through a single injection of lipopolysaccharide (LPS). Mice were then subsequently randomly allocated to either the luteolin or vehicle-treated group, then motor performance and dopaminergic neuronal injury were evaluated. BV2 microglial cells were treated with luteolin or vehicle saline prior to LPS challenge. MRNA expression of microglial specific marker ionized calcium-binding adapter molecule 1 (IBA-1) and M1/M2 polarization markers, as well as the abundance of indicated pro-inflammatory cytokines in the mesencephalic tissue and BV2 were quantified by real time-polymerase chain reaction (RT-PCR) and Enzyme-linked Immunosorbent Assay (ELISA), respectively. Cell viability and apoptosis of neuron-like PC12 cell line co-cultured with BV2 were detected. TLR4 RNA transcript and protein abundance in mesencephalic tissue and BV2 cells were detected. Nuclear factor kappa-gene binding (NF-κB) p65 subunit phosphorylation both in vitro and in vivo was evaluated by immunoblotting. Results: Luteolin treatment induced functional improvements and alleviated dopaminergic neuronal loss in the PD model. Luteolin inhibited apoptosis and promoted cell survival in PC12 cells. Luteolin treatment shifted microglial M1/M2 polarization towards an anti-inflammatory M2 phenotype both in vitro and in vivo. Finally, it was found that luteolin treatment significantly downregulated both TLR4 mRNA and protein expression as well as restraining NF-κB p65 subunit phosphorylation. Conclusions: Luteolin restrained dopaminergic degeneration in vitro and in vivo by blocking TLR4-mediated neuroinflammation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
薛wen晶完成签到 ,获得积分10
1秒前
taizaizi发布了新的文献求助10
2秒前
666发布了新的文献求助10
2秒前
小糯米发布了新的文献求助10
4秒前
4秒前
汪洋浮萍一道开完成签到,获得积分10
4秒前
4秒前
科研通AI2S应助美丽电源采纳,获得10
4秒前
坚定幻嫣关注了科研通微信公众号
5秒前
传统的钧发布了新的文献求助10
7秒前
充电宝应助科研通管家采纳,获得30
8秒前
斯文败类应助科研通管家采纳,获得10
8秒前
科研通AI2S应助科研通管家采纳,获得30
8秒前
Akim应助科研通管家采纳,获得10
8秒前
8秒前
8秒前
9秒前
自然的沛凝完成签到,获得积分20
9秒前
穆紫应助hitagi采纳,获得10
9秒前
9秒前
生姜完成签到,获得积分10
9秒前
唐秋秋发布了新的文献求助10
9秒前
cliche发布了新的文献求助10
10秒前
JIAO发布了新的文献求助10
11秒前
希望天下0贩的0应助Sun采纳,获得10
11秒前
11秒前
深海soda完成签到,获得积分10
12秒前
丘比特应助666采纳,获得10
12秒前
搜集达人应助123采纳,获得10
13秒前
14秒前
14秒前
15秒前
wjz完成签到,获得积分10
16秒前
Jasper应助酷炫的面包采纳,获得10
17秒前
Lucas应助蓉儿采纳,获得10
17秒前
年轻半雪发布了新的文献求助10
17秒前
YUgg发布了新的文献求助20
18秒前
小黄鸭发布了新的文献求助10
18秒前
高分求助中
Sustainability in Tides Chemistry 2000
Bayesian Models of Cognition:Reverse Engineering the Mind 800
Essentials of thematic analysis 700
A Dissection Guide & Atlas to the Rabbit 600
Very-high-order BVD Schemes Using β-variable THINC Method 568
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3124803
求助须知:如何正确求助?哪些是违规求助? 2775148
关于积分的说明 7725553
捐赠科研通 2430633
什么是DOI,文献DOI怎么找? 1291291
科研通“疑难数据库(出版商)”最低求助积分说明 622121
版权声明 600328