| 2'-Hydroxycinnamaldehyde targets low-density lipoprotein receptor-related protein-1 to inhibit lipopolysaccharide-induced microglial activation. | |
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MedLine Citation:
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PMID: 20933287 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Heehong Hwang; Hyejin Jeon; Jiyeon Ock; Su Hyung Hong; Young-Min Han; Byoung-Mog Kwon; Won-Ha Lee; Myung-Shik Lee; Kyoungho Suk |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-08 |
Journal Detail:
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Title: Journal of neuroimmunology Volume: 230 ISSN: 1872-8421 ISO Abbreviation: J. Neuroimmunol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109498 Medline TA: J Neuroimmunol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 52-64 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, Daegu, Republic of Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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