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Review
. 2024 Jan 22:15:1333006.
doi: 10.3389/fphar.2024.1333006. eCollection 2024.

Exploring Chinese herbal medicine for ischemic stroke: insights into microglia and signaling pathways

Wenjing Zhang  1 , Haoqun Xu  1 , Chong Li  1 , Bingbing Han  1 , Yimin Zhang  1
Affiliations
Review

Exploring Chinese herbal medicine for ischemic stroke: insights into microglia and signaling pathways

Wenjing Zhang et al. Front Pharmacol. .

Abstract

Ischemic stroke is a prevalent clinical condition affecting the central nervous system, characterized by a high mortality and disability rate. Its incidence is progressively rising, particularly among younger individuals, posing a significant threat to human well-being. The activation and polarization of microglia, leading to pro-inflammatory and anti-inflammatory responses, are widely recognized as pivotal factors in the pathogenesis of cerebral ischemia and reperfusion injury. Traditional Chinese herbal medicines (TCHMs) boasts a rich historical background, notable efficacy, and minimal adverse effects. It exerts its effects by modulating microglia activation and polarization, suppressing inflammatory responses, and ameliorating nerve injury through the mediation of microglia and various associated pathways (such as NF-κB signaling pathway, Toll-like signaling pathway, Notch signaling pathway, AMPK signaling pathway, MAPK signaling pathway, among others). Consequently, this article focuses on microglia as a therapeutic target, reviewing relevant pathway of literature on TCHMs to mitigate neuroinflammation and mediate IS injury, while also exploring research on drug delivery of TCHMs. The ultimate goal is to provide new insights that can contribute to the clinical management of IS using TCHMs.

Keywords: drug-delivery systems; inflammatory response; ischemic stroke; microglia; natural compounds in traditional Chinese herbal medicines; signaling pathway.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The NF-κB signaling pathway and Toll signaling pathway exert regulatory effects on microglia during the management of ischemic stroke. By suppressing microglial activation, these pathways can effectively impede the transition from microglia to M1 phenotype or facilitate the polarization from M1 to M2 phenotype, consequently safeguarding cerebral nerves and diminishing the secretion of inflammatory mediators. In this context, red signifies inhibition, while green signifies promotion.
FIGURE 2
FIGURE 2
The Notch signaling pathway, AMPK signaling pathway and MAPK signaling pathway exert regulatory effects on microglia during the management of ischemic stroke. By suppressing microglial activation, these pathways can effectively impede the transition from microglia to M1 phenotype or facilitate the polarization from M1 to M2 phenotype, consequently safeguarding cerebral nerves and diminishing the secretion of inflammatory mediators. In this context, red signifies inhibition, while green signifies promotion.
FIGURE 3
FIGURE 3
Other relevant signaling pathways play a crucial role in modulating the functioning of microglia during the treatment of ischemic stroke. By suppressing microglial activation, these pathways can effectively impede the transition from microglia to M1 phenotype or facilitate the polarization from M1 to M2 phenotype, consequently safeguarding cerebral nerves and diminishing the secretion of inflammatory mediators. In this context, red signifies inhibition, while green signifies promotion.
FIGURE 4
FIGURE 4
The mechanism by which traditional Chinese herbal medicines (TCHMs) traverse the BBB. Employing techniques such as receptor-mediated transcytosis (RMT), carrier-mediated transcytosis (CMT), and absorptive-mediated transcytosis (AMT) can facilitate the passage of TCHMs across the BBB, leading to a substantial enhancement in their bioavailability.
FIGURE 5
FIGURE 5
The regulatory effect of TCHMs on microglial response to cerebral ischemia. After cerebral ischemia and reperfusion, microglia immediately sense the disorder of brain homeostasis, and are activated and polarized. The M1 phenotype of polarized microglia is associated with the pro-inflammatory response of microglia to cerebral ischemic injury, while the M2 phenotype promotes anti-inflammatory response and brain repair. TCHMs can regulate these microglial responses by inhibiting M1 phenotype-related signaling pathways and molecular targets and enhancing M2 phenotype-related pathways, thereby reducing cerebral ischemic injury and promoting nervous system repairation.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Natural Science Foundation of Shandong Province (ZR2020KH003), the Jinan University Institute Innovation Team Project (2020GXRC012), and the Shandong University of Traditional Chinese Medicine Youth Innovation Team Project (2020-54-19).

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