PDF(Pubmed)
Abstract：
UNASSIGNED: Uremic toxin indoxyl sulfate (IS) induces vascular inflammation, a crucial event in renal failure, and vascular complications in patients with chronic kidney disease (CKD). In endothelial cells, IS increases the production of inflammatory cytokines partially via the activation of the aryl hydrocarbon receptor (AhR), and several food flavonoids have been reported to act as antagonists of AhR.
UNASSIGNED: This study aimed to investigate whether antagonistic flavonoids can attenuate IS-induced inflammatory responses in vascular endothelial cells in vitro and renal failure in vivo.
UNASSIGNED: Human umbilical vein endothelial cells (HUVECs) pretreated with the flavones apigenin, chrysin, or luteolin were stimulated with IS. Expression levels of genes involved in AhR signaling, inflammatory cytokine production, and reactive oxygen species (ROS) production were analyzed. Uninephrectomized mice were orally administered chrysin and received daily intraperitoneal injections of IS for 4 weeks.
UNASSIGNED: In HUVECs, IS upregulated the mRNA expression of AhR-targeted genes (CYP1A1 and AhRR), and genes involved in inflammation (NOX4, MCP-1, IL-6, and COX2) and monocyte invasion/adhesion (ICAM1). All three flavones attenuated the IS-induced increase in the expression of these mRNAs. They also suppressed the IS-induced nuclear translocation of AhR and intracellular ROS production. Furthermore, IS-induced phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was inhibited by treatment with these flavones. The results of in-vivo experiments showed that administration with chrysin attenuated the elevation of blood urea nitrogen levels and AhR-target gene expression and the pathological impairment of renal tissues in mice, regardless of higher serum levels of IS.
UNASSIGNED: Natural food flavones antagonizing AhR exerted protective effects against IS-induced inflammation through the inhibition of the AhR-STAT3 pathway in HUVECs. Moreover, chrysin ameliorated IS-induced renal dysfunction in a mouse model of CKD. These flavonoids could be a therapeutic strategy for vascular inflammation in CKD.
UNASSIGNED: This study aimed to investigate whether antagonistic flavonoids can attenuate IS-induced inflammatory responses in vascular endothelial cells in vitro and renal failure in vivo.
UNASSIGNED: Human umbilical vein endothelial cells (HUVECs) pretreated with the flavones apigenin, chrysin, or luteolin were stimulated with IS. Expression levels of genes involved in AhR signaling, inflammatory cytokine production, and reactive oxygen species (ROS) production were analyzed. Uninephrectomized mice were orally administered chrysin and received daily intraperitoneal injections of IS for 4 weeks.
UNASSIGNED: In HUVECs, IS upregulated the mRNA expression of AhR-targeted genes (CYP1A1 and AhRR), and genes involved in inflammation (NOX4, MCP-1, IL-6, and COX2) and monocyte invasion/adhesion (ICAM1). All three flavones attenuated the IS-induced increase in the expression of these mRNAs. They also suppressed the IS-induced nuclear translocation of AhR and intracellular ROS production. Furthermore, IS-induced phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was inhibited by treatment with these flavones. The results of in-vivo experiments showed that administration with chrysin attenuated the elevation of blood urea nitrogen levels and AhR-target gene expression and the pathological impairment of renal tissues in mice, regardless of higher serum levels of IS.
UNASSIGNED: Natural food flavones antagonizing AhR exerted protective effects against IS-induced inflammation through the inhibition of the AhR-STAT3 pathway in HUVECs. Moreover, chrysin ameliorated IS-induced renal dysfunction in a mouse model of CKD. These flavonoids could be a therapeutic strategy for vascular inflammation in CKD.
摘要：
■尿毒症毒素硫酸吲哚酚（IS）诱导血管炎症，肾功能衰竭的关键事件，慢性肾脏病（CKD）患者的血管并发症。在内皮细胞中，IS部分通过芳香烃受体（AhR）的激活增加炎性细胞因子的产生，据报道，几种食物类黄酮可作为AhR的拮抗剂。
■本研究旨在研究拮抗性黄酮类化合物是否可以减轻体外血管内皮细胞IS诱导的炎症反应和体内肾衰竭。
■用黄酮芹菜素预处理的人脐静脉内皮细胞，chrysin,或木犀草素用IS刺激。参与AhR信号传导的基因的表达水平，炎性细胞因子的产生，和活性氧（ROS）的产生进行了分析。经单切除小鼠经口施用chrysin，并每天腹膜内注射IS，持续4周。
■在HUVEC中，上调AhR靶向基因（CYP1A1和AhRR）的mRNA表达，和参与炎症的基因（NOX4，MCP-1，IL-6和COX2）和单核细胞侵袭/粘附（ICAM1）。所有三种黄酮均减弱了IS诱导的这些mRNA表达的增加。它们还抑制了IS诱导的AhR核易位和胞内ROS产生。此外，IS诱导的信号转导和转录激活因子3（STAT3）的磷酸化被这些黄酮处理抑制。体内实验结果表明，用chrysin减轻了小鼠血尿素氮水平和AhR靶基因表达的升高以及肾组织的病理损害，无论IS的血清水平是否较高。
■拮抗AhR的天然食物黄酮通过抑制HUVECs中的AhR-STAT3通路对IS诱导的炎症发挥保护作用。此外，在CKD小鼠模型中，chrysin改善了IS诱导的肾功能障碍。这些类黄酮可能是CKD血管炎症的治疗策略。
■本研究旨在研究拮抗性黄酮类化合物是否可以减轻体外血管内皮细胞IS诱导的炎症反应和体内肾衰竭。
■用黄酮芹菜素预处理的人脐静脉内皮细胞，chrysin,或木犀草素用IS刺激。参与AhR信号传导的基因的表达水平，炎性细胞因子的产生，和活性氧（ROS）的产生进行了分析。经单切除小鼠经口施用chrysin，并每天腹膜内注射IS，持续4周。
■在HUVEC中，上调AhR靶向基因（CYP1A1和AhRR）的mRNA表达，和参与炎症的基因（NOX4，MCP-1，IL-6和COX2）和单核细胞侵袭/粘附（ICAM1）。所有三种黄酮均减弱了IS诱导的这些mRNA表达的增加。它们还抑制了IS诱导的AhR核易位和胞内ROS产生。此外，IS诱导的信号转导和转录激活因子3（STAT3）的磷酸化被这些黄酮处理抑制。体内实验结果表明，用chrysin减轻了小鼠血尿素氮水平和AhR靶基因表达的升高以及肾组织的病理损害，无论IS的血清水平是否较高。
■拮抗AhR的天然食物黄酮通过抑制HUVECs中的AhR-STAT3通路对IS诱导的炎症发挥保护作用。此外，在CKD小鼠模型中，chrysin改善了IS诱导的肾功能障碍。这些类黄酮可能是CKD血管炎症的治疗策略。
