Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
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IF 3.9
Yu Ling,Luo Qianwen,Rao Xiaohui,Xiao Xiao,Wang Pinghan
Kawasaki disease (KD) is a severe pediatric vasculitis leading to coronary artery complications. Hydrogen sulfide (H 2 S), a recognized endogenous gasotransmitter with anti-inflammatory properties, offers potential as a novel treatment for KD through its cardiovascular benefits. However, the specific effects and underlying mechanisms remain unclear. The objective of present study is to investigate the anti-inflammatory and therapeutic effects of exogenous H 2 S in KD using network pharmacology and experimental validation. By online database searches, a total of 405 pharmacological targets for H 2 S, 826 KD-related targets, and 107 potential therapeutic targets of H 2 S for KD were identified. Through PPI analysis and Cytoscape screening, 9 hub genes were filtered, namely TNF, IL6, JUN, AKT1, IL1B, TP53, NFKB1, MAPK1, and RELA. KEGG pathway enrichment indicated that the TLR4/MyD88/NF-κB signaling pathway may play a crucial role in the therapeutic effects of H 2 S on KD. Additionally, in vivo experiments confirmed that the treatment of sodium hydrosulfide (NaHS), an H 2 S donor, markedly improved body weight, reduced inflammatory pathology in the coronary arteries, and downregulated levels of inflammatory cytokines TNF-α, IL-1β, and IL-6. Furthermore, WB analysis confirmed that NaHS inhibited the expression of TLR4, MyD88, NF-κB, and p-NF-κB. In brief, it is the first to reveal that exogenous H 2 S attenuates the inflammatory response in KD via the TLR4/MyD88/NF-κB pathway, highlighting its potential as a novel therapeutic approach for KD. These findings lay a foundation for further development of H 2 S-based therapies for KD management.
研究领域:
儿科
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药理学
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免疫学
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心血管科学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2025
·
IF 5.4
Yuting Guan,Jinghua Ruan,Pingping Tan,Songwei Qian,Size Zhou,Ao Zhang,Yuchong Fu,Shuhui Zhao,Yuqing Ran,Xing Feng,Yijia Wang,Xinlei Wu,Bing Zhang,Weiping Ji,Lianpin Wu,Xiaoling Guo
Kawasaki Disease (KD) is an acute and self-limiting vasculitis of unknown etiology that mainly occurs in infancy and can lead to vascular endothelial injury. Hesperidin (HES) is an economical dietary biological flavonoid with anti-oxidant, anti-inflammatory, and anti-apoptotic pharmacological effects. The main objective of this study was to investigate the protective effects of HES on KD, and try to elucidate the underlying mechanism. The Candida albicans water-soluble fraction (CAWS) was used to induce coronary arteritis of KD mouse model in vivo , and tumor necrosis factor α (TNF-α) was employed to induce human umbilical vein endothelial cell (HUVEC) injury of KD cell model in vitro to investigate the anti-inflammatory and anti-apoptotic effects of HES on KD. Our in vivo results showed that HES significantly reduced coronary artery injury in KD mice by alleviating pericoronary inflammatory infiltration and tissue fibrosis, inhibiting inflammatory cytokines and chemokine expressions, and decreasing vascular endothelial cell apoptosis. Our in vitro study confirmed that HES had the opposite ability of the NF-κB agonist NF-ĸB activator 1 (ACT1) to significantly alleviate the inflammatory response, CellROX level, and apoptosis by decreasing BAX/BCL-2 and Cleaved Caspase-3 levels as well as reducing TUNEL positive cells and the ratio of flow cytometric apoptotic cells in TNF-α induced HUVECs. The further mechanism study based on bioinformatics analysis and western blotting demonstrated that HES could protect against vascular inflammation and cell apoptosis of KD through inhibiting the TLR4/IĸBα/NF-ĸB pathway, suggesting that HES may be a promising therapeutic candidate for KD.
研究领域:
免疫学
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药理学
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分子生物学
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血管医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Wu Huilan,Wang Yijia,Tan Pingping,Ran Yuqing,Guan Yuting,Qian Songwei,Feng Xing,Jiang Yalan,Peng Yongmiao,Sheng Ke,Xi Haitao,Ji Weiping,Guo Xiaoling
Background: Kawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including anti-inflammatory, anti-apoptosis, and anti-fibrosis, and so on. So far, the protective effects of FA on KD have not been explored.Methods: In this study, we established Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model and the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model to investigate the anti-inflammatory and anti-apoptosis effects of FA on KD, and try to elucidate the underlying mechanism.Results: Our in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. In addition, Our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC). The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition.Conclusion: In conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future.
研究领域:
药理学
·
免疫学
·
血管生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）