Piceatannol ameliorates diabetic retinopathy mediated by microglial polariza-tion via inhibition of the CXCR4/BTK pathway
10.13389/j.cnki.rao.2025.0160
- VernacularTitle:白皮杉醇通过抑制CXCR4/BTK通路改善小胶质细胞极化介导的糖尿病视网膜病变
- Author:
Haiyan SUN
1
;
Yu ZHAI
1
;
Yuanqing ZHANG
1
;
Jiaxuan ZHANG
1
;
Zepeng ZHANG
1
;
Zhipeng YAN
1
;
Yun ZHANG
1
Author Information
1. 050000 河北省石家庄市,河北医科大学第三医院眼病科
- Publication Type:Journal Article
- Keywords:
piceatannol;
diabetic retinopathy;
microglial cells;
C-X-C motif chemokine receptor 4;
Bruton's tyrosine kinase
- From:
Recent Advances in Ophthalmology
2025;45(12):930-937
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether Piceatannol(PIC)improves diabetic retinopathy(DR)mediated by microglial polarization and to elucidate the underlying molecular mechanisms.Methods Network pharmacology and bioinformatics were used to analyze the common targets of DR,PIC,and microglia.Human retinal vascular endothelial cells(HRVECs)were cultured in vitro and randomly divided into the NG-HRVECs group,HG-HRVECs group,and HG+PIC-HRVECs group.Cell viability was assessed by the CCK-8 assay,apoptosis was detected by the TUNEL assay,and the concentrations of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured using ELISA kits.BV-2 cells were cultured in vitro and randomly divided into the NG-BV-2 group,HG-BV-2 group,HG+PIC-BV-2 group,HG+Si-NC-BV-2 group,HG+Si-CXCR4-BV-2 group,and HG+Ibrutinib-BV-2 group.The levels of arginase-1(Arg-1)and inducible ni-tric oxide synthase(iNOS)were measured using ELISA kits.Furthermore,conditioned medium(CM)from BV-2 cells of each group was collected to treat HRVECs,after which the viability,apoptosis rate,and TNF-α and IL-6 concentrations of the HRVECs were measured.A DR rat model was established and intervened with PIC to investigate the ameliorative effects of PIC on retinal pathology.Results Bioinformatics analysis identified CXCR4 as the key target of this study.Compared with the NG-HRVECs group,the apoptosis rate and the concentrations of TNF-α and IL-6 were increased in the HG-HRVECs group.Compared with the HG-HRVECs group,the HG+PIC-HRVECs group showed a decreased apoptosis rate and reduced concentrations of TNF-α and IL-6(all P＜0.05).Compared with the NG-BV-2 group,the HG-BV-2 group ex-hibited decreased Arg-1 levels and increased iNOS levels.Compared with the HG-BV-2 group,the HG+PIC-BV-2,HG+Si-CXCR4-BV-2,and HG+Ibrutinib-BV-2 groups all showed increased Arg-1 levels and decreased iNOS levels(all P＜0.05).Compared with the NG-BV-2-CM group,the HG-BV-2-CM group led to decreased viability,increased apoptosis rate,and in-creased concentrations of TNF-α and IL-6 in HRVECs.In contrast,the HG+PIC-BV-2-CM,HG+Si-CXCR4-BV-2-CM,and HG+Ibrutinib-BV-2-CM groups reversed the effects induced by HG-BV-2-CM on HRVECs(all P＜0.05).Animal experiment results showed that compared with DR model rats,rats treated with different doses of PIC exhibited significantly ameliora-ted retinal histopathological damage,and the protein expressions of Arg-1,iNOS,CXCR4,and p-BTK were reversed.Con-clusion PIC ameliorates DR progression mediated by microglial polarization by inhibiting the CXCR4/BTK pathway.
