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草药化合物,特别关注天麻素作为潜在的治疗剂用于小胶质细胞介导的神经炎症。

Herbal Compounds with Special Reference to Gastrodin as Potential Therapeutic Agents for Microglia Mediated Neuroinflammation.

机构信息

Department of Anatomy and Histology/Embryology, Kunming Medical University, 1168 West Chunrong Road, Kunming, China.

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

Curr Med Chem. 2018;25(42):5958-5974. doi: 10.2174/0929867325666180214123929.

Abstract

BACKGROUND

Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin- 1beta (IL-1β) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes.

METHODS

In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia. In this connection, the phenolic glucoside gastrodin, a main constituent of the Chinese herbal medicine Gastrodia rhizoma, produced widely in the local community exhibits potential neuroprotective effects through suppression of neurotoxic proinflammatory mediators.

RESULTS

Here, we first review the roles of activated microglia in different brain diseases. The effects of gastrodin on activated microglia are then considered. We have identified gastrodin as a putative therapeutic agent as it has been found to suppress microglial activation thus ameliorating neuroinflammation. More importantly, gastrodin downregulates the expression of renin angiotensin system (RAS) and production of proinflammatory mediators. Remarkably, gastrodin promotes Sirtuin 3 (Sirt3) up-regulation and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX-2) down-regulation after ischemichypoxia in activated microglia mediated by AT1 or AT2 receptors which are angiotensin II receptors subtypes, indicating a possible molecular link between RAS and Sirt3 survival genes.

CONCLUSION

This review summarizes the beneficial effects of gastrodin acting on activated microglia along with other herbal compounds. Its efficacy in neuroprotection is consistent with some common herbal products in China.

摘要

背景

激活的小胶质细胞通过产生多种促炎介质,如肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和一氧化氮(NO),在神经退行性疾病中发挥关键作用,这些介质对神经元和少突胶质细胞有毒性。

方法

鉴于上述情况,抑制小胶质细胞介导的神经炎症被认为是神经退行性疾病的一种治疗策略。已有报道称,几种潜在的中草药提取物针对激活的小胶质细胞,具有针对神经退行性疾病的神经保护作用。在这方面,酚苷天麻素是中草药天麻的主要成分之一,在当地社区广泛生产,通过抑制神经毒性促炎介质,显示出潜在的神经保护作用。

结果

在这里,我们首先回顾了激活的小胶质细胞在不同脑疾病中的作用。然后考虑了天麻素对激活的小胶质细胞的影响。我们已经确定天麻素是一种潜在的治疗剂,因为它已被发现可抑制小胶质细胞激活,从而改善神经炎症。更重要的是,天麻素下调肾素血管紧张素系统(RAS)的表达和促炎介质的产生。值得注意的是,天麻素在缺血缺氧后通过 AT1 或 AT2 受体(血管紧张素 II 受体亚型)促进激活的小胶质细胞中 Sirtuin 3(Sirt3)的上调和烟酰胺腺嘌呤二核苷酸磷酸氧化酶-2(NOX-2)的下调,表明 RAS 和 Sirt3 生存基因之间可能存在分子联系。

结论

本综述总结了天麻素作用于激活的小胶质细胞以及其他草药化合物的有益作用。其在神经保护方面的功效与中国一些常见的草药产品一致。

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