Scutellarin attenuates neuronal apoptosis in ischemic stroke rats via JAK2/STAT3 signaling pathway
10.3969/j.issn.1000-4718.2025.06.006
- VernacularTitle:灯盏乙素通过JAK2/STAT3信号通路减轻缺血性脑卒中大鼠神经元凋亡
- Author:
Zhaoda DUAN
1
;
Yingqi PENG
;
Dongyao XU
;
Yuke WU
;
Yujia YANG
;
Li YANG
;
Chunyun WU
Author Information
1. 昆明医科大学基础医学院人体解剖与组织胚胎学系,云南 昆明 650500;昆明医科大学生物医学工程研究院,云南 昆明 650500
- Publication Type:Journal Article
- Keywords:
scutellarin;
ischemic stroke;
neuronal apoptosis;
JAK2/STAT3 signaling pathway;
network phar-macology
- From:
Chinese Journal of Pathophysiology
2025;41(6):1098-1108
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To determine if scutellarin(Scu)provides neuroprotection by reducing neuronal apoptosis in rats subjected to middle cerebral artery occlusion(MCAO)via the inhibition of the JAK2/STAT3 signalling pathway.METHODS:Proteins linked to Scu and ischaemic stroke-induced neuronal apoptosis were identified using the Swiss Tar-get Prediction,PharmMapper,OMIM,and GeneCards databases.Intersecting targets were identified through Venn analy-sis.Protein-protein interaction networks were visualised utilising Cytoscape software,and principal targets were identi-fied.Enrichment analyses of GO functions and KEGG pathways were conducted utilising the Metascape database.Molecu-lar docking of Scu with core targets was performed utilising AutoDock Vina.The neuroprotective effects of Scu were as-sessed in MCAO rats using Zea Longa scoring and the suspension test.JAK2/STAT3 phosphorylation levels and apoptosis-related proteins[cleaved caspase-3(C-caspase-3),caspase-3,Bax,and Bcl-2]were assessed using Western blot and im-munofluorescence staining.The JAK2-specific inhibitor AG490 was employed to further investigate the role of the JAK2/STAT3 signaling pathway.RESULTS:Network pharmacology analysis revealed 832 shared targets,with pathways en-riched in tumor-associated pathways,the JAK/STAT signalling pathway,and the HIF-1 signalling pathway.Molecular docking revealed robust binding affinities of Scu with the ten principal targets.Behavioural assessments utilising Zea Lon-ga scoring and the suspension test demonstrated that Scu markedly enhanced neurological recovery in MCAO rats.Western blot and immunofluorescence analyses demonstrated that phosphorylation levels of JAK2 and STAT3,along with the ex-pression of C-caspase-3,Bax,and Bcl-2,were markedly elevated in the MCAO group relative to the sham group(P<0.05).Post Scu treatment,phosphorylation levels of JAK2 and STAT3,along with C-caspase-3 and Bax expression,were markedly diminished,whereas Bcl-2 expression and fluorescence intensity were substantially increased(P<0.05).In the combined AG490 and Scu treatment group(MCAO+Scu+AG490),the phosphorylation levels of JAK2 and STAT3,as well as the expression of C-caspase-3 and Bax,exhibited no significant difference when compared to the Scu-alone group(P>0.05).Bcl-2 expression and fluorescence intensity were markedly reduced in the combined AG490 and Scu treatment group relative to the Scu-alone group(P<0.05).CONCLUSION:Scu seems to provide neuroprotection in ischaemic stroke by reducing neuronal apoptosis through the inhibition of the JAK2/STAT3 signalling pathway.
