Background

Development of clinically effective neuroprotective agents for stroke therapy is still a challenging task. Microglia play a critical role in brain injury and recovery after ischemic stroke. Traditional Chinese herbal medicines (TCHMs) are based on a unique therapeutic principle, have various formulas, and have long been widely used to treat stroke. Therefore, the active compounds in TCHMs and their underlying mechanisms of action are attracting increasing attention in the field of stroke drug development.

Purpose

To summarize the regulatory mechanisms of TCHM-derived natural compounds on the microglial response in animal models of ischemic stroke.

Methods

We searched studies published until 10 April 2023 in the Web of Science, PubMed, and ScienceDirect using the following keywords: natural compounds, natural products or phytochemicals, traditional Chinese Medicine or Chinese herbal medicine, microglia, and ischemic stroke. This review was prepared according to PRISMA (Preferred Reporting Item for Systematic Reviews and Meta-Analysis) guidelines.

Results

Natural compounds derived from TCHMs can attenuate the M1 phenotype of microglia, which is involved in the detrimental inflammatory response, via inhibition of NF-κB, MAPKs, JAK/STAT, Notch, TLR4, P2X7R, CX3CR1, IL-17RA, the NLRP3 inflammasome, and pro-oxidant enzymes. Additionally, the neuroprotective response of microglia with the M2 phenotype can be enhanced by activating Nrf2/HO-1, PI3K/AKT, AMPK, PPARγ, SIRT1, CB2R, TREM2, nAChR, and IL-33/ST2. Several clinical trials showed that TCHM-derived natural compounds that regulate microglial responses have significant and safe therapeutic effects, but further well-designed clinical studies are needed.

Conclusions

Further research regarding the direct targets and potential pleiotropic or synergistic effects of natural compounds would provide a more reasonable approach for regulation of the microglial response with the possibility of successful stroke drug development.

中文翻译：

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中草药天然化合物对缺血性中风小胶质细胞反应的调节机制

背景

开发用于中风治疗的临床有效的神经保护剂仍然是一项具有挑战性的任务。小胶质细胞在缺血性中风后的脑损伤和恢复中发挥着关键作用。中草药治疗原理独特，配方多样，长期以来被广泛用于治疗中风。因此，中药中的活性化合物及其潜在作用机制在中风药物开发领域引起了越来越多的关注。

目的

总结中药来源的天然化合物对缺血性中风动物模型中小胶质细胞反应的调节机制。

方法

我们使用以下关键词检索了截至 2023 年 4 月 10 日在 Web of Science、PubMed 和 ScienceDirect 上发表的研究：天然化合物、天然产物或植物化学物质、中药或中草药、小胶质细胞和缺血性中风。本综述是根据 PRISMA（系统评价和荟萃分析的首选报告项目）指南编写的。

结果

源自 TCHM 的天然化合物可以通过抑制 NF-κB、MAPK、JAK/STAT、Notch、TLR4、P2X7R、CX3CR1、IL-17RA、NLRP3 炎症小体来减弱参与有害炎症反应的小胶质细胞的 M1 表型和促氧化酶。此外，具有M2表型的小胶质细胞的神经保护反应可以通过激活Nrf2/HO-1、PI3K/AKT、AMPK、PPARγ、SIRT1、CB2R、TREM2、nAChR和IL-33/ST2来增强。多项临床试验表明，中草药衍生的调节小胶质细胞反应的天然化合物具有显着且安全的治疗效果，但还需要进一步精心设计的临床研究。

结论

关于天然化合物的直接靶点和潜在多效性或协同效应的进一步研究将为调节小胶质细胞反应提供更合理的方法，并有可能成功开发中风药物。