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Background <p>The purpose of this study was to evaluate the therapeutic effects of Chrysin on endothelial inflammation in a KD mouse model and to elucidate the molecular mechanisms underlying these effects, with a particular focus on the NFAT2 signaling pathway.</p> Methods and results <p>In vivo, a KD mouse model was used to assess the effects of Chrysin on coronary artery inflammation. Histological analysis, immunohistochemistry, and cytokine profiling were performed to evaluate inflammatory cell infiltration, structural changes in the arteries, and modulation of key inflammatory cytokines. In vitro, TNFα-stimulated HCAECs were used to examine the protective effects of Chrysin on endothelial injury, including cytokine secretion and adhesion molecule expression. Mechanistic studies were conducted to explore the role of the NFAT2 signaling pathway in mediating Chrysin’s effects, utilizing molecular docking analysis and Western blotting. In vivo, Chrysin treatment significantly alleviated coronary artery inflammation in the KD mouse model. Histological analysis revealed reduced inflammatory cell infiltration and improved elastin fiber structure. Cytokine analysis showed that Chrysin attenuated the elevated levels of IL-6, IL-17, TNFα, and MCP-1 in KD mice. In vitro, Chrysin reduced TNFα-induced endothelial injury, as evidenced by decreased secretion of IL-6, IL-8, IL-23, ICAM-1 and VCAM-1 in HCAECs. Mechanistic investigations revealed that Chrysin’s effects on endothelial inflammation were mediated through the NFAT2 signaling pathway, rather than the upstream PLCγ1 pathway, as confirmed by molecular docking and Western blotting. Inhibition of PLCγ1 did not alter the protective effects of Chrysin, suggesting that its action is primarily through NFAT2.</p> Conclusions <p>This study provides the first evidence that Chrysin significantly reduces endothelial inflammation and vascular injury in KD. The observed anti-inflammatory effects are mediated through the NFAT2 signaling pathway, highlighting the potential of Chrysin as a therapeutic agent for managing KD and its associated vascular complications.</p>

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Chrysin improves endothelial inflammation via the NFAT pathway in Kawasaki disease

  • 期刊论文

  • 发表日期：

    2025年4月26日

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  • Jin Ma,
  • Yan Li,
  • Yunjia Tang,
  • Guanghui Qian,
  • Haitao Lv,
  • Xiudao Song,
  • Ying Liu

摘要

Background

The purpose of this study was to evaluate the therapeutic effects of Chrysin on endothelial inflammation in a KD mouse model and to elucidate the molecular mechanisms underlying these effects, with a particular focus on the NFAT2 signaling pathway.

Methods and results

In vivo, a KD mouse model was used to assess the effects of Chrysin on coronary artery inflammation. Histological analysis, immunohistochemistry, and cytokine profiling were performed to evaluate inflammatory cell infiltration, structural changes in the arteries, and modulation of key inflammatory cytokines. In vitro, TNFα-stimulated HCAECs were used to examine the protective effects of Chrysin on endothelial injury, including cytokine secretion and adhesion molecule expression. Mechanistic studies were conducted to explore the role of the NFAT2 signaling pathway in mediating Chrysin’s effects, utilizing molecular docking analysis and Western blotting. In vivo, Chrysin treatment significantly alleviated coronary artery inflammation in the KD mouse model. Histological analysis revealed reduced inflammatory cell infiltration and improved elastin fiber structure. Cytokine analysis showed that Chrysin attenuated the elevated levels of IL-6, IL-17, TNFα, and MCP-1 in KD mice. In vitro, Chrysin reduced TNFα-induced endothelial injury, as evidenced by decreased secretion of IL-6, IL-8, IL-23, ICAM-1 and VCAM-1 in HCAECs. Mechanistic investigations revealed that Chrysin’s effects on endothelial inflammation were mediated through the NFAT2 signaling pathway, rather than the upstream PLCγ1 pathway, as confirmed by molecular docking and Western blotting. Inhibition of PLCγ1 did not alter the protective effects of Chrysin, suggesting that its action is primarily through NFAT2.

Conclusions

This study provides the first evidence that Chrysin significantly reduces endothelial inflammation and vascular injury in KD. The observed anti-inflammatory effects are mediated through the NFAT2 signaling pathway, highlighting the potential of Chrysin as a therapeutic agent for managing KD and its associated vascular complications.