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Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses
Eun-Ju Yang1, Sae-Kwang Ku, Wonhwa Lee
1College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu, 702-701, Republic of Korea.
Aim And Objective:
The ubiquitous nuclear protein, high-mobility group box 1 (HMGB1), is released by activated macrophages and human umbilical vein endothelial cells (HUVECs) and functions as a late mediator of experimental sepsis. Polyozellin, which has been reported to have a variety of biological activities including antioxidant and anticancer activity, is the major active compound found in edible mushroom (Polyozellus multiplex). In this study, we investigated the antiseptic effects and underlying mechanisms of polyozellin against HMGB1-mediated septic responses in HUVECs and mice.
Methods:
The anti-inflammatory activities of polyozellin were determined by measuring permeability, human neutrophil adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice.
Results:
According to the results, polyozellin effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, polyozellin suppressed the production of tumor necrosis factor-α and interleukin (IL)-6, and the activation of nuclear factor-κB and extracellular signal-regulated kinases 1/2 by HMGB1.
Conclusion:
Collectively, these results indicate that P. multiplex containing polyozellin could be commercialized as functional food for preventing and treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
Insights
Polyozellin from edible mushrooms effectively combats sepsis by inhibiting high-mobility group box 1 (HMGB1) signaling. This compound reduces inflammation and vascular permeability, offering potential as a functional food for severe vascular inflammatory diseases.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- High-mobility group box 1 (HMGB1) is a nuclear protein released by activated cells, acting as a late mediator in experimental sepsis.
- Polyozellin, a compound from the edible mushroom *Polyozellus multiplex*, exhibits antioxidant and anticancer properties.
Purpose of the Study:
- To investigate the antiseptic effects of polyozellin against HMGB1-mediated septic responses.
- To elucidate the underlying mechanisms of polyozellin's action in human umbilical vein endothelial cells (HUVECs) and mice.
Main Methods:
- Assessed anti-inflammatory activities by measuring permeability, neutrophil adhesion, and migration in HMGB1-activated HUVECs and mice.
- Evaluated the impact of polyozellin on proinflammatory protein activation.
Main Results:
- Polyozellin inhibited lipopolysaccharide (LPS)-induced HMGB1 release and suppressed HMGB1-mediated septic responses, including hyperpermeability and leukocyte migration.
- Polyozellin reduced the production of tumor necrosis factor-α and interleukin-6, and inhibited nuclear factor-κB and extracellular signal-regulated kinases 1/2 activation.
Conclusions:
- Polyozellin demonstrates significant antiseptic effects by inhibiting the HMGB1 signaling pathway.
- *Polyozellus multiplex* containing polyozellin shows potential for commercialization as a functional food to prevent and treat severe vascular inflammatory diseases.
