期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 10, 期 4, 页码 493-499出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2010.01.011
关键词
Brain inflammation; Genipin; Interleukin-1 beta; Microglia; Nitric oxide; Prostaglandin; TNF-alpha
资金
- Ministry for Health & Welfare & Family Affairs, Republic of Korea [B090039]
- Korea Health Promotion Institute [B090039] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Microglia are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of various disorders in traditional oriental medicine. Genipin has recently been reported to have diverse pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The specific aim of this study was to examine whether genipin represses brain microglial activation. Genipin was effective at inhibiting LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells. Genipin reduced the LPS-stimulated production of tumor necrosis factor-alpha, interleukin-1 beta, prostaglandin E-2, intracellular reactive oxygen species, and NF-kappa B activation. In addition, genipin reduced NO release from microglia stimulated with interferon-gamma and amyloid-beta. Both pretreatment and post-treatment of genipin to LPS-stimulated microglia were effective at decreasing NO release. Furthermore, genipin effectively inhibited microglial activation in a mouse model of brain inflammation. These results suggest that genipin provide neuroprotection by reducing the production of various neurotoxic molecules from activated microglia. (C) 2010 Elsevier B.V. All rights reserved.
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