Regulatory mechanisms of natural compounds from traditional Chinese herbal medicines on the microglial response in ischemic stroke

Myong Hak Ri; Yue Xing; Hong Xiang Zuo; Ming Yue Li; Hong Lan Jin; Juan Ma; Xuejun Jin

doi:10.1016/j.phymed.2023.154889

Regulatory mechanisms of natural compounds from traditional Chinese herbal medicines on the microglial response in ischemic stroke

Phytomedicine. 2023 Jul 25:116:154889. doi: 10.1016/j.phymed.2023.154889. Epub 2023 May 20.

Authors

Myong Hak Ri¹, Yue Xing², Hong Xiang Zuo², Ming Yue Li², Hong Lan Jin², Juan Ma³, Xuejun Jin⁴

Affiliations

¹ Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Faculty of Life Science, Kim Il Sung University, Pyongyang, Democratic People's Republic of Korea.
² Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
³ Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: majuan@ybu.edu.cn.
⁴ Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: xjjin@ybu.edu.cn.

PMID: 37262999
DOI: 10.1016/j.phymed.2023.154889

Abstract

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.

Keywords: Ischemic stroke; Microglia; Natural compound; Neuroinflammation; Traditional Chinese herbal medicine.

Publication types

Review

MeSH terms

Animals
Brain Ischemia* / drug therapy
Ischemic Stroke* / drug therapy
Microglia
Phosphatidylinositol 3-Kinases
Plant Extracts / pharmacology
Stroke* / drug therapy

Substances

Phosphatidylinositol 3-Kinases
Plant Extracts