Mechanism of tanshinone ⅡA and scutellarin in synergistically ameliorating ischemic stroke via inhibition of the PKCδ/NLRC4/Caspase-1 pathway
YAN Yuxuan
YUE Jiao
JIANG Yongli
HU Lining
JIN Yuchen
HE Ran
LU Yujie
LU Beining
GUO Qingjuan
LIU Chenxu
LIU Zixuan
WANG Xinshang
LIU Shuibing
Abstract：Objective To investigate the synergistic neuroprotective effects of tanshinone ⅡA(Tan ⅡA)and scutellarin(Scu)on ischemic stroke and explore the underlying molecular mechanisms.Methods Primary neurons were cultured in vitro.A glutamate(Glu)-induced excitotoxicity model was established to preliminarily screen neuroprotective monomeric compounds from traditional Chinese medicine,followed by validation using a H2O2-induced oxidative stress injury model.A mouse model of photothrombotic stroke(PTS)was constructed to investigate the synergistic in vivo protective effects of Tan ⅡA and Scu.Neurological function and tissue damage were assessed using neurological deficit scores,TTC staining,HE staining,and Nissl staining.Molecular mechanisms were explored via RNA sequencing,Western blotting,ELISA,and qRT-PCR.Results In vitro,either Tan ⅡA or Scu significantly alleviated neuronal damage caused by Glu or H2O2.In vivo,combined administration of Tan ⅡA and Scu significantly reduced neurological deficit scores,decreased infarct volume,and mitigated neuronal damage in PTS model mice,with effects superior to either monotherapy.RNA sequencing analysis revealed that combined treatment significantly downregulated Prkcd gene expression.Molecular biological assays confirmed that the combination therapy synergistically inhibited the PKCδ/NLRC4/Caspase-1 signaling pathway,reduced levels of pro-inflammatory factors such as IL-1β and IL-18,and attenuated neuroinflammatory responses.Conclusion Tan ⅡA and Scu exert synergistic neuroprotective effects by inhibiting the PKCδ/NLRC4/Caspase-1 signaling pathway-mediated neuroinflammation,providing a novel therapeutic strategy for ischemic stroke.
Keywords：ischemic stroketanshinone ⅡAflavonoidsneuroprotectionneuroinflammatory diseasesprotein kinase C-deltaCaspase-1disease modelsanimal
Publication Date：2026-02-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：11( 273-283 )