Hirsutine, an indole alkaloid of Uncaria rhynchophylla, inhibits inflammation-mediated neurotoxicity and microglial activation
Hirsutine, an indole alkaloid of Uncaria rhynchophylla, inhibits inflammation-mediated neurotoxicity and microglial activation
复制标题
DOI：
10.3892/mmr.2012.1135
复制
发表时间：
2013-01-01
影响因子：
3.4
通讯作者：
Lee, Eunjoo H.
中科院分区：
文献类型：
--
作者：
Jung, Hwan Yong;Nam, Kyong Nyon;Lee, Eunjoo H.
慢性小胶质细胞激活通过释放各种促炎和神经毒性因子危及神经元存活。因此，小胶质细胞激活的负调节因子被认为是降低与炎症相关的神经变性风险的潜在治疗候选者。钩藤（U. rhynchophylla）是一种传统的东方草药，已被用于治疗心血管和中枢神经系统的疾病。毛茸碱（HS）是一种主要的吲哚类生物碱，具有神经保护作用。本研究的目的是研究HS在抑制炎症诱导的神经毒性和小胶质细胞活化方面的功效。在器官型海马切片培养中，HS阻断了脂多糖（LPS）相关的海马细胞死亡和一氧化氮（NO）、前列腺素（PG） E-2和白细胞介素-1 β的产生。HS可有效抑制lps诱导的大鼠脑小胶质细胞NO释放。该化合物减少了lps刺激的PGE(2)和细胞内活性氧的产生。HS显著降低了lps诱导的丝裂原活化蛋白激酶和Akt信号蛋白的磷酸化。综上所述，HS减少了激活的小胶质细胞中各种神经毒性因子的产生，并在炎症诱导的神经毒性模型中具有神经保护活性。
Chronic microglial activation endangers neuronal survival through the release of various pro-inflammatory and neurotoxic factors. As such, negative regulators of microglial activation have been considered as potential therapeutic candidates to reduce the risk of neurodegeneration associated with inflammation. Uncaria rhynchophylla (U. rhynchophylla) is a traditional oriental herb that has been used for treatment of disorders of the cardiovascular and central nervous systems. Hirsutine (HS), one of the major indole alkaloids of U. rhynchophylla, has demonstrated neuroprotective potential. The aim of the present study was to examine the efficacy of HS in the repression of inflammation-induced neurotoxicity and microglial cell activation. In organotypic hippocampal slice cultures, HS blocked lipopolysaccharide (LPS)-related hippocampal cell death and production of nitric oxide (NO), prostaglandin (PG) E-2 and interleukin-1 beta. HS was demonstrated to effectively inhibit LPS-induced NO release from cultured rat brain microglia. The compound reduced the LPS-stimulated production of PGE(2) and intracellular reactive oxygen species. HS significantly decreased LPS-induced phosphorylation of the mitogen-activated protein kinases and Akt signaling proteins. In conclusion, HS reduces the production of various neurotoxic factors in activated microglial cells and possesses neuroprotective activity in a model of inflammation-induced neurotoxicity.