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Sinomenine alleviates neuroinflammation in chronic cerebral hypoperfusion by promoting M2 microglial polarization and inhibiting neuronal pyroptosis via exosomal miRNA-223-3p.

作者信息

Yang Qu, Chen Qi, Zhang Kai-Bing, Liu Yu, Zheng Jia-Cheng, Hu Dong-Xia, Luo Jun

机构信息

Department of Rehabilitation Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.

Jiangxi Province Key Laboratory of Precision Cell Therapy, Nanchang, Jiangxi, 330006, China.

出版信息

Acta Neuropathol Commun. 2025 Mar 5;13(1):48. doi: 10.1186/s40478-025-01950-z.


DOI:10.1186/s40478-025-01950-z
PMID:40045356
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11881310/
Abstract

Chronic cerebral hypoperfusion (CCH) is a major contributor to vascular dementia, with neuroinflammation playing a central role in its pathogenesis. Sinomenine (SINO), a natural alkaloid derived from traditional Chinese medicine, has shown significant anti-inflammatory and neuroprotective properties. However, its efficacy and mechanism of action in CCH remain unclear. In this study, we established a CCH rat model through bilateral common carotid artery occlusion and administered 10 mg/kg of SINO daily. Behavioral tests demonstrated that SINO significantly improved cognitive and memory functions in CCH rats. Histological analysis revealed that SINO effectively reduced neuroinflammation and damage in the hippocampal CA1, CA3, and DG regions. Mechanistically, SINO promoted microglial polarization from the M1 to M2 phenotype, markedly inhibiting the release of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Further exploration of its neuroprotective mechanism showed that exosomes from SINO-treated microglia were enriched with miRNA-223-3p, which suppressed NLRP3-mediated pyroptosis in neurons. While our findings highlight the therapeutic potential of SINO, further studies are needed to validate its safety and efficacy in diverse populations and chronic settings. In summary, this study not only demonstrates SINO's regulatory effect on microglial polarization in CCH but also unveils a novel neuroprotective mechanism through exosomal miRNA-223-3p delivery, providing a solid theoretical foundation for SINO's potential as a treatment for CCH.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/b3566fbcf075/40478_2025_1950_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/62bafea3f9b8/40478_2025_1950_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/47578b6c33b3/40478_2025_1950_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/e3e0ea9c49bd/40478_2025_1950_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/f40f7e1726cc/40478_2025_1950_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/146cc248aff4/40478_2025_1950_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/7201abc8ef03/40478_2025_1950_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/a25730f205d0/40478_2025_1950_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/b3566fbcf075/40478_2025_1950_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/62bafea3f9b8/40478_2025_1950_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/47578b6c33b3/40478_2025_1950_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/e3e0ea9c49bd/40478_2025_1950_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/f40f7e1726cc/40478_2025_1950_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/146cc248aff4/40478_2025_1950_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/7201abc8ef03/40478_2025_1950_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/a25730f205d0/40478_2025_1950_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44b5/11881310/b3566fbcf075/40478_2025_1950_Fig8_HTML.jpg

相似文献

[1]
Sinomenine alleviates neuroinflammation in chronic cerebral hypoperfusion by promoting M2 microglial polarization and inhibiting neuronal pyroptosis via exosomal miRNA-223-3p.

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[3]
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J Neuroinflammation. 2025-6-17

[7]
[ cultured calculus bovis alleviates cerebral ischemia/reperfusion injury through regulating microglial polarization and inhibiting NLRP3].

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[8]
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[9]
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[10]
Tomatidine attenuates post-stroke cognitive impairment by reducing neuroinflammation through prevention of M1 microglial polarization via NF-κB signaling.

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本文引用的文献

[1]
The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors.

Br J Pharmacol. 2023-10

[2]
ChemR23 activation attenuates cognitive impairment in chronic cerebral hypoperfusion by inhibiting NLRP3 inflammasome-induced neuronal pyroptosis.

Cell Death Dis. 2023-11-6

[3]
From mundane to classic: Sinomenine as a multi-therapeutic agent.

Br J Pharmacol. 2025-5

[4]
Pharmacological mechanisms of sinomenine in anti-inflammatory immunity and osteoprotection in rheumatoid arthritis: A systematic review.

Phytomedicine. 2023-12

[5]
Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model.

Adv Sci (Weinh). 2023-11

[6]
Vascular cognitive impairment - Past, present, and future challenges.

Ageing Res Rev. 2023-9

[7]
A review on the current literature regarding the value of exosome miRNAs in various diseases.

Ann Med. 2023-12

[8]
microRNAs in action: biogenesis, function and regulation.

Nat Rev Genet. 2023-12

[9]
Chronic cerebral hypoperfusion: a critical feature in unravelling the etiology of vascular cognitive impairment.

Acta Neuropathol Commun. 2023-6-12

[10]
Distinctive role of inflammation in tissue repair and regeneration.

Arch Pharm Res. 2023-2

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