3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses
<b>Background/Objectives:</b> Phytochemicals are increasingly recognized for their therapeutic potential in treating various diseases, including vascular disorders. High mobility group box 1 (HMGB1), a key mediator of late-stage sepsis, triggers the release of proinflammatory cytokines,...
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MDPI AG
2025-05-01
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| author | Jinhee Lee Gyuri Han Jong-Sup Bae |
| author_facet | Jinhee Lee Gyuri Han Jong-Sup Bae |
| author_sort | Jinhee Lee |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Phytochemicals are increasingly recognized for their therapeutic potential in treating various diseases, including vascular disorders. High mobility group box 1 (HMGB1), a key mediator of late-stage sepsis, triggers the release of proinflammatory cytokines, leading to inflammation and systemic complications. Elevated plasma levels of HMGB1 impair diagnosis and prognosis while worsening outcomes in inflammatory conditions. 3-deoxysappanchalcone (3-DSC), a compound derived from <i>Biancaea sappan</i> (L.) Tod., has demonstrated anti-influenza and anti-allergic effects, though its role in HMGB1-mediated severe vascular inflammation remains unclear. This study hypothesized that 3-DSC could modulate lipopolysaccharide-induced HMGB1 activity and its downstream inflammatory pathways in human umbilical vein endothelial cells (HUVECs). <b>Methods</b>: In vitro and in vivo permeability; cell viability, adhesion, and excavation of leukocytes; the development of cell adhesion molecules; and lastly, the production of proinflammatory substances were investigated on human endothelial cells and mouse disease models to investigate the efficacy of 3-DSC in inflammatory conditions. <b>Results</b>: Experiments revealed that 3-DSC inhibited HMGB1 translocation from HUVECs, reduced neutrophil adhesion and extravasation, suppressed HMGB1 receptor formation, and blocked nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) synthesis. <b>Conclusions</b>: These findings suggest that 3-DSC effectively mitigates HMGB1-driven inflammation, offering promise as a therapeutic candidate for inflammatory diseases. |
| format | Article |
| id | doaj-art-f3427cdd32b14483bfb1ea49dd828f3c |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-f3427cdd32b14483bfb1ea49dd828f3c2025-08-20T03:47:58ZengMDPI AGPharmaceuticals1424-82472025-05-0118573110.3390/ph180507313-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory ResponsesJinhee Lee0Gyuri Han1Jong-Sup Bae2College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaCollege of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaCollege of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea<b>Background/Objectives:</b> Phytochemicals are increasingly recognized for their therapeutic potential in treating various diseases, including vascular disorders. High mobility group box 1 (HMGB1), a key mediator of late-stage sepsis, triggers the release of proinflammatory cytokines, leading to inflammation and systemic complications. Elevated plasma levels of HMGB1 impair diagnosis and prognosis while worsening outcomes in inflammatory conditions. 3-deoxysappanchalcone (3-DSC), a compound derived from <i>Biancaea sappan</i> (L.) Tod., has demonstrated anti-influenza and anti-allergic effects, though its role in HMGB1-mediated severe vascular inflammation remains unclear. This study hypothesized that 3-DSC could modulate lipopolysaccharide-induced HMGB1 activity and its downstream inflammatory pathways in human umbilical vein endothelial cells (HUVECs). <b>Methods</b>: In vitro and in vivo permeability; cell viability, adhesion, and excavation of leukocytes; the development of cell adhesion molecules; and lastly, the production of proinflammatory substances were investigated on human endothelial cells and mouse disease models to investigate the efficacy of 3-DSC in inflammatory conditions. <b>Results</b>: Experiments revealed that 3-DSC inhibited HMGB1 translocation from HUVECs, reduced neutrophil adhesion and extravasation, suppressed HMGB1 receptor formation, and blocked nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) synthesis. <b>Conclusions</b>: These findings suggest that 3-DSC effectively mitigates HMGB1-driven inflammation, offering promise as a therapeutic candidate for inflammatory diseases.https://www.mdpi.com/1424-8247/18/5/7313-deoxysappanchalconebarrier integrityLPSHMGB1endothelium |
| spellingShingle | Jinhee Lee Gyuri Han Jong-Sup Bae 3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses Pharmaceuticals 3-deoxysappanchalcone barrier integrity LPS HMGB1 endothelium |
| title | 3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses |
| title_full | 3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses |
| title_fullStr | 3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses |
| title_full_unstemmed | 3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses |
| title_short | 3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses |
| title_sort | 3 deoxysappanchalcone inhibited high mobility group box protein 1 mediated severe inflammatory responses |
| topic | 3-deoxysappanchalcone barrier integrity LPS HMGB1 endothelium |
| url | https://www.mdpi.com/1424-8247/18/5/731 |
| work_keys_str_mv | AT jinheelee 3deoxysappanchalconeinhibitedhighmobilitygroupboxprotein1mediatedsevereinflammatoryresponses AT gyurihan 3deoxysappanchalconeinhibitedhighmobilitygroupboxprotein1mediatedsevereinflammatoryresponses AT jongsupbae 3deoxysappanchalconeinhibitedhighmobilitygroupboxprotein1mediatedsevereinflammatoryresponses |