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菖蒲抑制小胶质细胞介导的神经炎症,预防 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病小鼠模型的神经毒性。

Acorus gramineus inhibits microglia mediated neuroinflammation and prevents neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease.

机构信息

Department of Biotechnology, College of Biomedical & Health Science, Reaearch Institute of Inflammatory Diseases, Konkuk University, Chungju 380-701, Republic of Korea.

出版信息

J Ethnopharmacol. 2012 Dec 18;144(3):506-13. doi: 10.1016/j.jep.2012.09.026. Epub 2012 Oct 17.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Acorus gramineus Solander (Acoraceae, AG), is a widely distributed plant in Asian countries. Rhizome part of this plant has long been used as a traditional medicine for treating various symptoms including central nervous system (CNS) disorders.

AIM OF STUDY

The anti-neuroinflammatory effect of AG aqueous extract was investigated using in vitro cellular and in vivo Parkinson's disease (PD) mouse model.

MATERIALS AND METHODS

Lipopolysaccharide (LPS) is used to stimulate BV-2 microglial cells in vitro and the changes in neuroinflammatory expressional levels were measured using ELISA, Western blotting, RT-PCR and immunofluorescence techniques. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD was developed followed by immunohistochemical analysis of specific brain tissues.

RESULTS

LPS-stimulation to BV-2 cells increased the production of nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β. Pretreatment with AG extract inhibited the increased levels of NO and pro-inflammatory cytokines in LPS-stimulated BV-2 cells. Mechanistic study revealed that AG acts via the regulation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and TRIF-dependent signaling pathways. Further, AG protected MPTP-induced neuronal cell death and inhibited neuroinflammation in vivo.

CONCLUSION

Our results indicated that AG extract exerted anti-neuroinflammatory effects against activated microglia mediated insults through multiple signaling pathways and prevented in vivo neuronal cell death in mouse model of PD substantiating the traditional claims for its use in CNS disorders.

摘要

民族药理学相关性

菖蒲(天南星科菖蒲属,AG)在亚洲国家广泛分布。该植物的根茎部分长期以来一直被用作传统药物,用于治疗各种症状,包括中枢神经系统(CNS)紊乱。

研究目的

本研究采用体外细胞和体内帕金森病(PD)小鼠模型研究 AG 水提物的抗炎作用。

材料和方法

脂多糖(LPS)用于体外刺激 BV-2 小胶质细胞,并通过 ELISA、Western blot、RT-PCR 和免疫荧光技术测量神经炎症表达水平的变化。在体内实验中,建立了 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 小鼠模型,随后对特定脑组织进行免疫组织化学分析。

结果

LPS 刺激 BV-2 细胞增加了一氧化氮(NO)和促炎细胞因子如肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6 和 IL-1β的产生。AG 提取物预处理抑制了 LPS 刺激的 BV-2 细胞中 NO 和促炎细胞因子水平的升高。机制研究表明,AG 通过调节核因子 kappa B(NF-κB)、丝裂原激活蛋白激酶(MAPKs)和 TRIF 依赖性信号通路发挥作用。此外,AG 可保护 MPTP 诱导的神经元细胞死亡,并抑制体内 PD 小鼠模型的神经炎症。

结论

我们的研究结果表明,AG 提取物通过多种信号通路对激活的小胶质细胞介导的损伤发挥抗炎作用,并防止 PD 小鼠模型中的体内神经元细胞死亡,这支持了其在 CNS 紊乱中的传统用途。

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