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Picropodophyllotoxin Mitigates Severe Inflammation Through HMGB1 Inhibition
Gyuri Han1, Ga Eun Kim1, Jong-Sup Bae1
1Research Institute of Pharmaceutical Sciences, Cellular & Molecular Research Institute (CMRI), College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea.
Biomolecules
|May 27, 2026
Summary
Picropodophyllotoxin (PPT) reduces HMGB1 release and inflammatory signaling in endothelial cells. This plant-derived compound shows promise for treating HMGB1-related vascular inflammation.
Area of Science:
- Vascular inflammation research
- Phytochemical pharmacology
- Sepsis and inflammatory mediators
Background:
- High mobility group box 1 (HMGB1) is a key mediator in sepsis-induced inflammation and vascular complications.
- Elevated HMGB1 levels correlate with poor prognosis in inflammatory conditions.
- Picropodophyllotoxin (PPT), a phytochemical, has demonstrated anti-cancer properties but its role in vascular inflammation is unknown.
Purpose of the Study:
- To investigate the effect of PPT on lipopolysaccharide (LPS)-induced HMGB1 activity.
- To explore PPT's influence on inflammatory signaling pathways in human umbilical vein endothelial cells (HUVECs).
Main Methods:
- In vitro studies using cultured HUVECs and in vivo mouse models.
- Assessment of endothelial barrier function, cell survival, and leukocyte interactions.
- Measurement of cell adhesion molecules and pro-inflammatory factor release.
Main Results:
- PPT significantly inhibited HMGB1 translocation and release from HUVECs.
- PPT reduced neutrophil adhesion and migration, and HMGB1 receptor expression.
- PPT suppressed nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) production.
Conclusions:
- PPT demonstrates potent anti-inflammatory effects by targeting multiple steps in the HMGB1-mediated inflammatory cascade.
- PPT inhibits HMGB1 release, receptor binding, NF-κB activation, and downstream cytokine production.
- PPT is a promising therapeutic candidate for HMGB1-related inflammatory diseases, warranting further investigation.
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