IMR Press / JIN / Volume 23 / Issue 11 / DOI: 10.31083/j.jin2311196
Open Access Original Research
Avicularin Treatment Ameliorates Ischemic Stroke Damage by Regulating Microglia Polarization and its Exosomes via the NLRP3 Pathway
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Affiliation
1 Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, 110032 Shenyang, Liaoning, China
2 Department of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, 110032 Shenyang, Liaoning, China
3 Teaching and Experiment Center, Liaoning University of Traditional Chinese Medicine, 110032 Shenyang, Liaoning, China
4 Department of Rehabilitation Medicine, The Second Hospital of Dalian Medical University, 116023 Dalian, Liaoning, China
*Correspondence: Z15566892865@163.com (Jinling Zheng)
These authors contributed equally.
J. Integr. Neurosci. 2024, 23(11), 196; https://doi.org/10.31083/j.jin2311196
Submitted: 2 July 2024 | Revised: 3 September 2024 | Accepted: 11 September 2024 | Published: 30 October 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract
Background:

Avicularin (AL), an ingredient of Banxia, has anti-inflammatory properties in cerebral disease and regulates polarization of macrophages, but its effects on ischemic stroke (IS) damage have not been studied.

Methods:

In vivo, AL was administered by oral gavage to middle cerebral artery occlusion/reperfusion (MCAO/R) C57BL/6J mice in doses of 1.25, 2.5, and 5 mg/kg/day for seven days, and, in vitro, AL was added to treat oxygen-glucose deprivation (OGD)-BV2 cells. Modified neurological severity score, Triphenyltetrazolium chloride (TTC) staining, brain-water-content detection, TdT-mediated dUTP nick-end labeling (TUNEL) assay, flow cytometry, immunofluorescence assay, Enzyme linked immunosorbent assay (ELISA), and Western-blot analysis were used to investigate the functions and mechanism of the effect of AL treatment on IS. The exosomes of AL-treated microglia were studied by transmission electron microscope (TEM), nanoparticle tracking analyzer (NTA), and Western-blot analysis.

Results:

AL treatment reduced the neurological severity score, infarct volume, brain-water content, neuronal apoptosis, and the release of inflammatory factors, that were induced by MCAO/R. Notably, M2 microglia polarization was promoted but M1 microglia polarization was inhibited by AL in the ischemic penumbra of MCAO/R mice. Subsequently, anti-inflammatory and polarization-regulating effects of AL were verified in vitro. Suppressed NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation was found in the ischemic penumbra of animal and Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) cells treated with AL, as evidenced by decreasing NLRP3-inflammasome-related protein and downstream factors. After AL treatment, the anti-apoptosis effect of microglial exosomes on OGD/R primary cortical neurons was increased.

Conclusion:

AL reduce inflammatory responses and neuron death of IS-associated models by regulating microglia polarization by the NLRP3 pathway and by affecting microglial exosomes.

Keywords
avicularin
ischemic stroke
microglial exosomes
microglia polarization
NLRP3
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Funding
ZYZX2207/ Open fund of Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine
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