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Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ

General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the...

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Autores principales: Ma, Jun, Zhang, Yuyang, Sugai, Takeshi, Kubota, Tetsuo, Keino, Hiroshi, El-Salhy, Magdy, Ozaki, Michitaka, Umezawa, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466912/
https://www.ncbi.nlm.nih.gov/pubmed/34571920
http://dx.doi.org/10.3390/cells10092271
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author Ma, Jun
Zhang, Yuyang
Sugai, Takeshi
Kubota, Tetsuo
Keino, Hiroshi
El-Salhy, Magdy
Ozaki, Michitaka
Umezawa, Kazuo
author_facet Ma, Jun
Zhang, Yuyang
Sugai, Takeshi
Kubota, Tetsuo
Keino, Hiroshi
El-Salhy, Magdy
Ozaki, Michitaka
Umezawa, Kazuo
author_sort Ma, Jun
collection PubMed
description General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases.
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spelling pubmed-84669122021-09-27 Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ Ma, Jun Zhang, Yuyang Sugai, Takeshi Kubota, Tetsuo Keino, Hiroshi El-Salhy, Magdy Ozaki, Michitaka Umezawa, Kazuo Cells Review General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases. MDPI 2021-09-01 /pmc/articles/PMC8466912/ /pubmed/34571920 http://dx.doi.org/10.3390/cells10092271 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ma, Jun
Zhang, Yuyang
Sugai, Takeshi
Kubota, Tetsuo
Keino, Hiroshi
El-Salhy, Magdy
Ozaki, Michitaka
Umezawa, Kazuo
Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ
title Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ
title_full Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ
title_fullStr Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ
title_full_unstemmed Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ
title_short Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ
title_sort inhibition of cellular and animal inflammatory disease models by nf-κb inhibitor dhmeq
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466912/
https://www.ncbi.nlm.nih.gov/pubmed/34571920
http://dx.doi.org/10.3390/cells10092271
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