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羌活根提取物(NRE)通过 TLR4-NF-κB 通路缓解阿尔茨海默病的神经炎症病理。

Notopterygium incisum roots extract (NRE) alleviates neuroinflammation pathology in Alzheimer's disease through TLR4-NF-κB pathway.

机构信息

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Key Laboratory of Pharmacodynamic Substances Research & Translational Medicine of Immune Diseases of Shenyang, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.

Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110840, People's Republic of China.

出版信息

J Ethnopharmacol. 2024 Dec 5;335:118651. doi: 10.1016/j.jep.2024.118651. Epub 2024 Jul 31.

DOI:10.1016/j.jep.2024.118651
PMID:39094757
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Notopterygium incisum Ting ex H. T. Chang, also called 'Qianghuo', is a distinct umbelliferae plant in China. The rhizomes and roots of Notopterygium incisum have long been used to treat headaches, colds, analgesia and rheumatoid arthritis. It is a main traditional Chinese medicine in Qianghuo Yufeng Decoction, which was used to treat diseases such as liver and kidney insufficiency, mental paralysis and dementia.

AIM OF THIS STUDY

As the most common dementia, Alzheimer's disease (AD) has a complicated pathogenesis. So far, there is no effective drug to prevent its pathological process. Previous research has shown that Notopterygium incisum root extract (NRE) may inhibit the release of Aβ and the activation of tau in mice with AD. However, the effect of NRE on the pathological process of neuroinflammation is still unclear.

MATERIALS AND METHODS

We determined the pro-inflammatory cytokines levels in BV2 cells exposed to LPS/Aβ42 after treated with NRE. APP/PS1 and LPS-induced C57BL/6 neuroinflammatory mice were given NRE for 8 weeks and 5 days respectively to detect the pathological changes of neuroinflammation.

RESULTS

The findings showed that NRE had a notable inhibitory effect on the levels of TNF-α and IL-1β in BV2 cells induced by LPS/Aβ42. The results of in vivo experiments show that following NRE treatment, there was a notable decrease in the number of activated microglia in the hippocampus of APP/PS1 mice as indicated by immunofluorescence results. Sholl analysis showed that microglia branches increased in NRE group, indicating that M1 microglia activation was inhibited. In the mice model injected with LPS in the tail vein, PCR and Western Blot results confirmed the anti-inflammatory effect of NRE, Nissl staining showed the protective effect of NRE on neurons, and immunofluorescence results also indicated that the activation of M1 microglia was inhibited.

CONCLUSION

These results suggest that long term oral administration of NRE may inhibit neuroinflammation in the progression of AD.

摘要

民族药理学相关性

羌活,伞形科羌活属植物,在中国是一种独特的伞形科植物。羌活的根茎和根一直被用于治疗头痛、感冒、止痛和类风湿性关节炎。羌活鱼风汤是一种主要的中药方剂,用于治疗肝肾不足、精神麻痹和痴呆等疾病。

研究目的

阿尔茨海默病(AD)是最常见的痴呆症,其发病机制复杂。到目前为止,还没有有效的药物可以预防其病理过程。先前的研究表明,羌活根提取物(NRE)可能抑制 AD 小鼠 Aβ的释放和 tau 的激活。然而,NRE 对神经炎症病理过程的影响尚不清楚。

材料和方法

我们测定了 LPS/Aβ42 作用后 BV2 细胞中促炎细胞因子的水平。用 NRE 分别处理 APP/PS1 和 LPS 诱导的 C57BL/6 神经炎症小鼠 8 周和 5 天,检测神经炎症的病理变化。

结果

结果表明,NRE 对 LPS/Aβ42 诱导的 BV2 细胞中 TNF-α和 IL-1β水平有显著的抑制作用。体内实验结果表明,NRE 处理后,APP/PS1 小鼠海马区激活的小胶质细胞数量明显减少,免疫荧光结果也证实了这一点。Sholl 分析表明,NRE 组小胶质细胞分支增加,表明 M1 型小胶质细胞激活受到抑制。在尾静脉注射 LPS 的小鼠模型中,PCR 和 Western Blot 结果证实了 NRE 的抗炎作用,Nissl 染色显示 NRE 对神经元有保护作用,免疫荧光结果也表明 M1 型小胶质细胞的激活受到抑制。

结论

这些结果表明,长期口服 NRE 可能抑制 AD 进展中的神经炎症。

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