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Inhibitory Functions of Novel Compounds from Dioscorea batatas Decne Peel on HMGB1-mediated Septic Responses

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  • Biomedical Engineering
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Abstract

Inhibition of high mobility group box 1 (HMGB1) signaling and restoration of endothelial integrity are emerging as promising therapeutic strategies for managing severe vascular inflammatory diseases. Dioscorea batatas Decne (DBD, Chinese yam), a perennial plant which belongs to Dioscoreaceae, is widely cultivated across Korea, Japan, China, and other tropical and subtropical regions, and both the aerial parts and roots of this plant are used for food and medicinal purposes. Here, we determined the effects of the two phenanthrene compounds from DBD peel, 2,7-dihydroxy-4,6-dimethoxyphenanthrene (1) and 6,7-dihydroxy-2,4-dimethoxyphenanthrene (2), on HMGB1-mediated septic responses and survival rate in cecal ligation and puncture (CLP)-induced septic model. The anti-inflammatory activities of compounds 1 and 2 were monitored by lipopolysaccharide (LPS)- or CLP-induced release of HMGB1. The anti-septic activities of compounds 1 and 2 were determined by measuring permeability, leukocyte adhesion and migration, and pro-inflammatory protein activation in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice. Compounds 1 and 2 inhibited HMGB1 release and downregulated HMGB1-mediated inflammatory responses in HUVECs. Compounds 1 and 2 also inhibited HMGB1-induced hyperpermeability and leukocyte migration in mice. Additionally, treatment with compounds 1 and 2 reduced CLP-induced HMGB1 release and sepsis-related mortality and pulmonary damage in vivo. Our results indicate that the compounds 1 and 2 are potential therapeutic agents for treating severe vascular inflammatory diseases via HMGB1 signaling pathway inhibition.

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Acknowledgements

This work was supported by a grant provided by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0001) and by the national Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2017R1A5A2015391).

The authors declare no conflict of interest.

Neither ethical approval nor informed consent was required for this study.

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Author notes

  1. First two authors contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu, 41566, Korea

    So Yeon Jeong & Jong-Sup Bae

  2. School of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, 41566, Korea

    Minyoul Kim, Jong-Sang Kim & Dongyup Hahn

  3. Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu, 41940, Korea

    Eui Kyun Park

  4. Institute of Agricultural Science and Technology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, 41566, Korea

    Jong-Sang Kim & Dongyup Hahn

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  1. So Yeon Jeong
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  2. Minyoul Kim
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Correspondence to Dongyup Hahn or Jong-Sup Bae.

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Jeong, S.Y., Kim, M., Park, E.K. et al. Inhibitory Functions of Novel Compounds from Dioscorea batatas Decne Peel on HMGB1-mediated Septic Responses. Biotechnol Bioproc E 25, 1–8 (2020). https://doi.org/10.1007/s12257-019-0382-1

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  • DOI: https://doi.org/10.1007/s12257-019-0382-1

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