Department of Medical Science, Graduate School of East-West Medical Science; Kyung Hee University, Yongin-si 446-701, South Korea.
Int Immunopharmacol. 2010 Apr;10(4):493-9. doi: 10.1016/j.intimp.2010.01.011. Epub 2010 Feb 1.
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-1beta, prostaglandin E(2), intracellular reactive oxygen species, and NF-kappaB 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.
小胶质细胞是中枢神经系统（CNS）免疫和炎症反应的主要效应细胞。在病理条件下，这些细胞的激活有助于恢复 CNS 的内稳态。然而，慢性小胶质细胞激活通过释放各种促炎和神经毒性因子而危及神经元存活。因此，小胶质细胞激活的负调节剂被认为是针对神经退行性变（如阿尔茨海默病和帕金森病）的潜在治疗候选物。栀子苷的苷元京尼平，在栀子果实中发现，长期以来一直被认为是治疗传统东方医学中各种疾病的药物。京尼平最近被报道具有多种药理作用，如抗菌、抗肿瘤和抗炎作用。本研究的具体目的是研究京尼平是否能抑制大脑小胶质细胞的激活。京尼平能有效抑制 LPS 诱导的大鼠脑小胶质细胞一氧化氮（NO）释放。京尼平降低了 LPS 刺激的肿瘤坏死因子-α、白细胞介素-1β、前列腺素 E（2）、细胞内活性氧和 NF-κB 激活的产生。此外，京尼平还降低了干扰素-γ和淀粉样β刺激的小胶质细胞中 NO 的释放。LPS 刺激的小胶质细胞的京尼平预处理和后处理均能有效降低 NO 释放。此外，京尼平在脑炎症的小鼠模型中能有效抑制小胶质细胞的激活。这些结果表明，京尼平通过减少激活的小胶质细胞产生各种神经毒性分子提供神经保护作用。
