Pushen capsule treatment promotes functional recovery after ischemic stroke

Yuan Zhang; Ling Shen; Jian Xie; Lu Li; Wen Xi; Bin Li; Ying Bai; Honghong Yao; Shenyang Zhang; Bing Han

doi:10.1016/j.phymed.2023.154664

Pushen capsule treatment promotes functional recovery after ischemic stroke

Phytomedicine. 2023 Mar:111:154664. doi: 10.1016/j.phymed.2023.154664. Epub 2023 Jan 11.

Authors

Yuan Zhang¹, Ling Shen¹, Jian Xie¹, Lu Li¹, Wen Xi¹, Bin Li¹, Ying Bai¹, Honghong Yao², Shenyang Zhang³, Bing Han⁴

Affiliations

¹ Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
² Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China; Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu, 210009, China. Electronic address: yaohh@seu.edu.cn.
³ Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China; Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: 230219417@seu.edu.cn.
⁴ Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China. Electronic address: hanb@seu.edu.cn.

PMID: 36682301
DOI: 10.1016/j.phymed.2023.154664

Abstract

Background: As a leading cause of long-term disability, ischemic stroke urgently needs further research and drug development. Pushen capsule (Pushen) has been commonly applied in clinical treatment for relieving headaches, dizziness, and numbness. However, the effects of Pushen on ischemic stroke have not been revealed yet.

Purpose: To assess the efficiency of Pushen in ischemic stroke and identify its potential therapeutic targets and active ingredients for treating ischemic stroke.

Study design and methods: Behavioural experiments, Triphenyltetrazolium chloride (TTC) staining, Magnetic resonance imaging (MRI), and immunofluorescence staining were performed to examine the efficiency of Pushen in stroke model mice. The potential mechanism and active ingredients of Pushen were assessed by transcriptome, 16S rDNA sequencing, metabonomics, and network pharmacology. Finally, the targets were validated by RT-PCR, chromatin immunoprecipitation (ChIP), ELISA, and molecular docking methods.

Results: Pushen had several effects on stroke model mice, including reducing the infarct volume, improving the blood‒brain barrier (BBB), and promoting functional restoration. Furthermore, the network pharmacology, LC-MS/MS, and molecular docking results revealed that tricin, quercetin, luteolin, kaempferol, and physcion were identified as the key active ingredients in Pushen that treated ischemic stroke. Mechanistically, these key ingredients could bind with the transcription factor c-Myc and thereby regulate the expression of Adora2a, Drd2, and Ppp1r1b, which are enriched in the cAMP signaling pathway. Additionally, Pushen improved the gut microbiota dysbiosis and reduced inosine levels in feces and serum, thereby reducing Adora2a expression in the brain.

Conclusions: Our study confirmed that Pushen was effective for treating ischemic stroke and has promising clinical applications.

Keywords: C-myc; Functional recovery; Ischemic stroke; Pushen capsule; Traditional Chinese medicine (TCM).

MeSH terms

Animals
Chromatography, Liquid
Drugs, Chinese Herbal* / pharmacology
Ischemic Stroke* / drug therapy
Mice
Molecular Docking Simulation
Stroke* / drug therapy
Tandem Mass Spectrometry

Substances

Drugs, Chinese Herbal