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Brain Res. 2018 Jan 15;1679:144-154. doi: 10.1016/j.brainres.2017.11.030. Epub 2017 Dec 1.

Madecassoside protects BV2 microglial cells from oxygen-glucose deprivation/reperfusion-induced injury via inhibition of the toll-like receptor 4 signaling pathway.

Author information

1
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
2
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China; School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
3
Department of Emergency, Chinese PLA General Hospital, Beijing 100853, China.
4
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: youzili@uestc.edu.cn.
5
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China. Electronic address: yonganw@126.com.

Abstract

In a previous study, the authors reported that madecassoside (MA) exerted a potent neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury in rats, mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. However, the cellular and molecular bases for its neuroprotective effects have not been fully elucidated. In this study, an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) was used to investigate the role of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway in the neuroprotective and anti-inflammatory effects of MA. BV2 microglia viability after OGD/R, treated with or without MA, was measured using the MTT assay. Messenger RNA and protein expression of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin-1β [IL-1β], interleukin-6 [IL-6]) were measured using real-time polymerase chain reaction (RT-PCR) and ELISA after OGD/R or lipopolysaccharide treatment. Expression of TLR4/MyD88 and NF-κB p65 were measured using RT-PCR, Western blotting, and immunofluorescence analysis. MA significantly rescued OGD/R-induced cytotoxicity in BV2 microglia. Meanwhile, MA suppressed the secretion of pro-inflammatory mediators, including TNF-α, IL-1β, and IL-6, induced by OGD/R or lipopolysaccharide in BV2 microglia. The mechanism of its neuroprotection and anti-inflammation from OGD/R may involve the inhibition of activation of TLR4 and MyD88 in BV2 microglia, and the blockage of NF-κB p65 nuclear translocation. MA exhibited a significant neuroprotective effect against I/R injury in both in vivo and in vitro experiments by attenuating microglia-mediated neuroinflammation via inhibition of the TLR4/MyD88/NF-κB signaling pathway.

KEYWORDS:

Inflammation; Madecassoside; Microglia; NF-κB; Oxygen-glucose deprivation/reperfusion (OGD/R); TLR4

PMID:
29198964
DOI:
10.1016/j.brainres.2017.11.030
[Indexed for MEDLINE]

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