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Title 

2'-Hydroxycinnamaldehyde targets low-density lipoprotein receptor-related protein-1 to inhibit lipopolysaccharide-induced microglial activation

 

하이드록시신남알데하이드가 LRP-1을 표적으로 신경세포에서 기능 조절

Authors 

H HwangH JeonJ OckS H HongYoung Min HanByoung-Mog KwonW H LeeM S LeeK Suk

Publisher 

Elsevier

Issue Date 

2011

Citation 

Journal of Neuroimmunology, vol. 230, no. 1, pp. 52-64

Keywords 

2′-HydroxycinnamaldehydeCentral nervous systemCytokinesLow-density lipoprotein receptor-related protein-1MacrophagesMicrogliaNeuroinflammationNeuroprotectionNitric oxide

Abstract 

2'-Hydroxycinnamaldehyde (HCA) isolated from the stem bark of Cinnamomum cassia and its derivative 2'-benzoyloxycinnamaldehyde (BCA) were reported to have anti-angiogenic, anti-proliferative, and anti-inflammatory effects in several human cancer cells and RAW 264.7 macrophage cells. However, effects of HCA/BCA on the neuroinflammation have not been investigated. In the present study, a potential anti-neuroinflammatory effect of HCA/BCA was assessed in lipopolysaccharide (LPS)-stimulated microglial cultures and microglia/neuroblastoma cocultures. Nitric oxide production, inflammatory gene expression, and signaling pathways were investigated. HCA/BCA significantly decreased the production of nitric oxide and tumor necrosis factor-alpha (TNF-α) in microglial cells. HCA/BCA also attenuated the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin-1β (IL-1β) and TNF-α at mRNA level via blockade of ERK, JNK, p38 MAPK, and NF-κB activation. Moreover, HCA/BCA was neuroprotective by reducing microglia-mediated neuroblastoma cell death in a microglia-neuroblastoma co-culture. Affinity chromatography and LC-MS/MS analysis identified low-density lipoprotein receptor-related protein 1 (LRP1) as a potential molecular target of HCA in microglial cells. Based on the studies using the receptor-associated protein (RAP) that blocks a ligand binding to LRP1 and the siRNA-mediated LRP1 gene silencing, we were able to conclude that HCA inhibited LPS-induced microglial activation via LRP1. Our results suggest that HCA/BCA be anti-inflammatory and neuroprotective in the CNS by targeting LRP1, and may have a therapeutic potential against neuroinflammatory diseases.

ISSN 

0165-5728

Link 

http://dx.doi.org/10.1016/j.jneuroim.2010.08.021

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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