Curcumin reduces neuroinflammation and oxidative stress in a stroke model by epigenetically regulating ADRB2 methylation through JAK2/STAT3 and Nrf2/HO-1 pathways

作者：Liangzhe Wei, He Ren, Mingyue Zhao, Tianqi Xu, Jianhong Yang, Xinpeng Deng, Jie Sun, Shengjun Zhou, Jianmin Zhang, Xiang Gao, Yi Huang · 发表于：Journal of Neuroinflammation · 年份：2026 · DOI：10.1186/s12974-026-03729-y · 被引用次数：3 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Curcumin's Biomedical Applications、Parkinson's Disease Mechanisms and Treatments

The pathological mechanism of acute ischemic stroke (AIS) is complex, and exploring new diagnostic biomarkers and key molecular pathological targets is crucial for improving patient prognosis. The role of epigenetic regulation, especially DNA methylation, in AIS is receiving increasing attention, but its key target genes and clinical translational value still need to be elucidated. This study included 90 case-control groups and used pyrophosphate sequencing to detect the methylation level of β2-adrenergic receptor (ADRB2) promoter in peripheral blood. Using oxygen glucose deprivation/reperfusion (OGD/R) cell models and middle cerebral artery occlusion (MCAO) mouse models, the effects of ADRB2 expression on JAK2/STAT3 and Nrf2/HO-1 pathways, as well as inflammatory and oxidative stress factors, were evaluated using Western blot, ELISA, and other techniques. Intervention study using curcumin. The ADRB2 promoter region in the peripheral blood of AIS patients showed significant hypermethylation, and its level was significantly negatively correlated with ADRB2 mRNA and protein expression. ROC curve analysis shows that the methylation level of specific CpG sites has extremely high predictive value for AIS diagnosis (AUC ≥ 0.9). Functional experiments have confirmed that DNMT1 mediated methylation of ADRB2 increases after ischemia and hypoxia, and the downregulation of ADRB2 protein directly leads to activation of the JAK2/STAT3 pathway and inhibition of the Nrf2/HO-1 pathway, there...