Comprehensive immune modulation mechanisms of Angong Niuhuang Wan in ischemic stroke: Insights from mass cytometry analysis

Author:

Yao Yang12,Ni Weihua1,Feng Liangshu1,Meng Jihong1,Tan Xiaomu1,Chen Hansen13ORCID,Shen Jiangang3ORCID,Zhao Heng14ORCID

Affiliation:

1. Department of Neurosurgery Stanford University School of Medicine Stanford California USA

2. Department of Neurology Tianjin Medical University General Hospital Tianjin China

3. School of Chinese Medicine, State Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong China

4. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Joint Innovation Center for Brain Disorders Capital Medical University Beijing China

Abstract

AbstractBackgroundAngong Niuhuang Wan (AGNHW, 安宫牛黄丸), is a classical medicinal formula in Traditional Chinese Medicine (TCM) that has been appreciated for its neuroprotective properties in ischemic cerebral injuries, yet its intricate mechanisms remain only partially elucidated.AimsThis study leverages advanced Mass cytometry (CyTOF) to analyze AGNHW's multifaceted immunomodulation effects in‐depth, emphasizing previously underexplored areas.ResultsAGNHW mitigated monocyte‐derived macrophages (MoDM) infiltration in the brain, distinguishing its effects on those from microglia. While the vehicle group exhibited elevated inflammatory markers like CD4, CD8a, and CD44 in ischemic brains, the AGNHW‐treated group attenuated their expressions, indicating AGNHW's potential to temper the post‐ischemic inflammatory response. Systemically, AGNHW modulated fundamental immune cell dynamics, notably augmenting CD8+ T cells, B cells, monocytes, and neutrophil counts in the peripheral blood under post‐stroke conditions. Intracellularly, AGNHW exhibited its targeted modulation of the signaling pathways, revealing a remarked inhibition of key markers like IκBα, indicating potential suppression of inflammatory responses in ischemic brain injuries.ConclusionThis study offers a comprehensive portrait of AGNHW's immunomodulation effects on ischemic stroke, illuminating its dual sites of action—both cerebral and systemic—and its nuanced modulation of cellular and molecular dynamics.

Publisher

Wiley

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