Genipin attenuates lipopolysaccharide-induced persistent changes of emotional behaviors and neural activation in the hypothalamic paraventricular nucleus and the central amygdala nucleus
Genipin attenuates lipopolysaccharide-induced persistent changes of emotional behaviors and neural activation in the hypothalamic paraventricular nucleus and the central amygdala nucleus
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DOI：
10.1016/j.ejphar.2014.07.038
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发表时间：
2014-10-15
影响因子：
5
通讯作者：
Yabe, Takeshi
中科院分区：
文献类型：
--
作者：
Araki, Ryota;Hiraki, Yosuke;Yabe, Takeshi
疾病行为是炎症性疾病（包括感染和癌症）中发生的一系列行为和心理变化。施用细菌内毒素脂多糖（LPS）会诱发啮齿动物的疾病行为。京尼平是从栀子果实中提取的环烯醚萜苷京尼平苷衍生的苷元，具有抗炎和抗抑郁活性。然而，京尼平对炎症引起的情绪行为变化的影响尚不清楚。在这项研究中，我们研究了京尼平对 LPS 诱导的 BV-2 细胞炎症和小鼠疾病行为的影响。京尼平预处理可抑制 BV-2 细胞中 LPS 诱导的 NO 产生增加，并降低炎症相关基因（iNOS、COX-2、IL-1β 和 IL-6）的 mRNA 水平。口服京尼平可改善小鼠强迫游泳测试中 LPS 诱导的抑郁样行为以及 LPS 给药 24 小时后的社交行为缺陷。 LPS 诱导的下丘脑室旁核 (PVN) 和杏仁核中央核 (CeA) 中炎症相关基因 mRNA 的表达和 c-fos 免疫阳性细胞的数量减少，表明京尼平通过抑制 PVN 和 CeA 中的神经激活和炎症反应来减弱 LPS 诱导的情绪行为变化。京尼平的这些新的药理作用可能有助于治疗有病态行为的患者。 (C) 2014 Elsevier B.V. 保留所有权利。
Sickness behavior is a series of behavioral and psychological changes that develop in inflammatory disease, including infections and cancers. Administration of the bacterial endotoxin lipopolysaccharide (LPS) induces sickness behavior in rodents. Genipin, an aglycon derived from an iridoid glycoside geniposide extracted from the fruit of Gardenia jasminoides, has anti-inflammatory and antidepressant activities. However, the effects of genipin on inflammation-induced changes in emotional behaviors are unknown. In this study, we examined the effects of genipin on LPS-induced inflammation in BV-2 cells and sickness behavior in mice. Pretreatment with genipin inhibited LPS-induced increases in NO production and reduced the mRNA levels of inflammation-related genes (iNOS, COX-2, IL-1 beta and IL-6) in BV-2 cells. Oral administration of genipin ameliorated LPS-induced depressive-like behavior in the forced swim test and social behavior deficits 24 h after LPS administration in mice. LPS-induced expression of mRNAs for inflammation-related genes and the number of c-fos immunopositive cells decreased in the paraventricular nucleus (PVN) of the hypothalamus and the central nucleus of the amygdala (CeA), suggesting that genipin attenuates LPS-induced changes of emotional behaviors through inhibition of neural activation and inflammatory responses in the PVN and CeA. These novel pharmacological effects of genipin may be useful for treatment of patients with sickness behavior. (C) 2014 Elsevier B.V. All rights reserved.