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Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses

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Abstract

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.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2012R1A5A2A42671316).

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    Authors and Affiliations

    1. College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu, 702-701, Republic of Korea

      Eun-Ju Yang, Wonhwa Lee, Kyung-Sik Song & Jong-Sup Bae

    2. Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea

      Sae-Kwang Ku

    3. BK21 Plus KNU Biomedical Convergence Program, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 702-701, Republic of Korea

      Wonhwa Lee

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    Eun-Ju Yang and Sae-Kwang Ku contributed equally to this work.

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    Yang, EJ., Ku, SK., Lee, W. et al. Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses. Inflamm. Res. 64, 733–746 (2015). https://doi.org/10.1007/s00011-015-0856-3

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