Quercetin attenuates acute inflammation and extracellular matrix remodeling after intracerebral hemorrhage: transcriptomics-informed network pharmacology and experimental validation
- 1The People’s Hospital of the Qiandongnan Miao and Dong Autonomous Prefecture
- 2Zunyi Medical University
- 3Guihang 300 Hospital Affiliated to Zunyi Medical University
Abstract
Intracerebral hemorrhage (ICH) induces secondary brain injury characterized by neuroinflammation, blood–brain barrier disruption, oxidative stress, and extracellular matrix (ECM) remodeling. Quercetin (QR), a natural flavonoid with anti-inflammatory and antioxidant activities, has shown neuroprotective potential; however, the molecular signatures associated with its effects in acute ICH remain incompletely defined. In this study, QR-related target prediction, ICH-associated gene mining, endoplasmic reticulum stress-related gene annotation, and 2 mouse brain transcriptomic datasets were integrated to prioritize QR-associated targets in ICH. Functional enrichment, protein–protein interaction, immune deconvolution, receiver operating characteristic (ROC), and molecular docking analyses were then performed. Key predictions were further evaluated in a collagenase-induced mouse ICH model treated with QR or dexamethasone for 24 h, and their disease relevance was assessed using paired perihematomal and remote brain tissues from ICH patients, with serum cytokine profiling performed in ICH patients and healthy controls. Twenty-nine candidate genes were identified and were mainly enriched in TNF and IL-17 signaling, leukocyte migration, stress-responsive programs, and ECM-associated processes. Seven consensus hub genes were prioritized, including Il1b , Mmp9 , Timp1 , Myc , Fos , Hmox1 , and Socs3 . Five hub genes in GSE113151 and six in GSE200575 showed high exploratory discriminative performance. Molecular docking suggested putative binding compatibility between QR and several hub proteins. In vivo , high-dose QR reduced brain water content after ICH. QR treatment suppressed perihematomal Il1b , Mmp9 , and Fos expression, increased Timp1 expression, and selectively upregulated Hmox1 at the high dose, while reducing circulating IL-1β, IL-6, TNF-α, and MMP-9 levels. In human ICH samples, perihematomal tissues showed increased IL1B , MMP9 , TIMP1 , and HMOX1 expression; Western blotting further showed increased IL-1β, MMP-9, and TIMP1 protein levels, and immunohistochemistry showed enhanced MMP-9 immunoreactivity. Circulating inflammatory cytokines were also elevated in patients with ICH. These findings suggest that QR is associated with attenuation of acute inflammatory and matrix-remodeling responses after experimental ICH, providing a pharmacological rationale for further target-focused mechanistic studies and long-term preclinical evaluation.
Related
- Shexiang Huayu Xingnao Granule Alleviates Intracerebral Hemorrhage via PI3K/AKT-Mediated Neuroinflammation Regulation: Integrated Network Pharmacology and Experimental Validation.
- Dihydroartemisinin alleviates allergic airway inflammation by suppressing the PI3K-AKT signaling axis: integrated network pharmacology and experimental validation.
- Artesunate attenuates inflammation and neurological impairment in intracerebral hemorrhage mice by inhibiting microglia NLRP3/ASC/Caspase-1
- Integrative transcriptomics and reverse network pharmacology prioritize DPP4 and Achyranthes bidentata in Barrett’s esophagus
- Network Pharmacology of Natural Products from Computational Prediction to Experimental Validation
BibTeX
@article{shu2026quercetin,
title = {{Quercetin attenuates acute inflammation and extracellular matrix remodeling after intracerebral hemorrhage: transcriptomics-informed network pharmacology and experimental validation}},
author = {Jun Shu and Kexin Feng and Anqi Pan and Gang Li and Kaifeng Liu and Luqian Feng},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1930434},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1930434/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Quercetin attenuates acute inflammation and extracellular matrix remodeling after intracerebral hemorrhage: transcriptomics-informed network pharmacology and experimental validation
AU - Jun Shu
AU - Kexin Feng
AU - Anqi Pan
AU - Gang Li
AU - Kaifeng Liu
AU - Luqian Feng
PY - 2026
DA - 2026/10/19
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1930434
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1930434/full
AB - Intracerebral hemorrhage (ICH) induces secondary brain injury characterized by neuroinflammation, blood–brain barrier disruption, oxidative stress, and extracellular matrix (ECM) remodeling. Quercetin (QR), a natural flavonoid with anti-inflammatory and antioxidant activities, has shown neuroprotective potential; however, the molecular signatures associated with its effects in acute ICH remain incompletely defined. In this study, QR-related target prediction, ICH-associated gene mining, endoplasmic reticulum stress-related gene annotation, and 2 mouse brain transcriptomic datasets were integrated to prioritize QR-associated targets in ICH. Functional enrichment, protein–protein interaction, immune deconvolution, receiver operating characteristic (ROC), and molecular docking analyses were then performed. Key predictions were further evaluated in a collagenase-induced mouse ICH model treated with QR or dexamethasone for 24 h, and their disease relevance was assessed using paired perihematomal and remote brain tissues from ICH patients, with serum cytokine profiling performed in ICH patients and healthy controls. Twenty-nine candidate genes were identified and were mainly enriched in TNF and IL-17 signaling, leukocyte migration, stress-responsive programs, and ECM-associated processes. Seven consensus hub genes were prioritized, including Il1b , Mmp9 , Timp1 , Myc , Fos , Hmox1 , and Socs3 . Five hub genes in GSE113151 and six in GSE200575 showed high exploratory discriminative performance. Molecular docking suggested putative binding compatibility between QR and several hub proteins. In vivo , high-dose QR reduced brain water content after ICH. QR treatment suppressed perihematomal Il1b , Mmp9 , and Fos expression, increased Timp1 expression, and selectively upregulated Hmox1 at the high dose, while reducing circulating IL-1β, IL-6, TNF-α, and MMP-9 levels. In human ICH samples, perihematomal tissues showed increased IL1B , MMP9 , TIMP1 , and HMOX1 expression; Western blotting further showed increased IL-1β, MMP-9, and TIMP1 protein levels, and immunohistochemistry showed enhanced MMP-9 immunoreactivity. Circulating inflammatory cytokines were also elevated in patients with ICH. These findings suggest that QR is associated with attenuation of acute inflammatory and matrix-remodeling responses after experimental ICH, providing a pharmacological rationale for further target-focused mechanistic studies and long-term preclinical evaluation.
SN - 1663-9812
ER -