Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3
Abstract Periodontitis is a chronic periodontal inflammatory disease caused by periodontal pathogens commonly seen in adults. Eupalinolide B (EB) is a sesquiterpenoid natural product extracted from Eupatorium lindleyanum and has been reported as a potential drug for cancers and immune disorders. Her...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.70034 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594224848044032 |
|---|---|
| author | Wenhua Kuang Ruishen Zhuge Ping Song Letai Yi Shujie Zhang Ying Zhang Yin Kwan Wong Ruixing Chen Junzhe Zhang Yuanbo Wang Dandan Liu Zipeng Gong Peili Wang Xiangying Ouyang Jigang Wang |
| author_facet | Wenhua Kuang Ruishen Zhuge Ping Song Letai Yi Shujie Zhang Ying Zhang Yin Kwan Wong Ruixing Chen Junzhe Zhang Yuanbo Wang Dandan Liu Zipeng Gong Peili Wang Xiangying Ouyang Jigang Wang |
| author_sort | Wenhua Kuang |
| collection | DOAJ |
| description | Abstract Periodontitis is a chronic periodontal inflammatory disease caused by periodontal pathogens commonly seen in adults. Eupalinolide B (EB) is a sesquiterpenoid natural product extracted from Eupatorium lindleyanum and has been reported as a potential drug for cancers and immune disorders. Here, we explored the ameliorative effects and underlying molecular mechanism of EB on periodontitis for the first time. We demonstrated that EB ameliorates periodontal inflammation and alveolar bone resorption with a ligated periodontitis mouse model. In addition, the impact of EB on macrophages inflammation was examined in the Raw264.7 cell line. We identified ubiquitin‐conjugating enzyme, UBE2D3, as the direct covalent binding protein targets of EB by using a chemoproteomic method based on activity‐based protein profiling, biolayer interferometry method, and cellular thermal shift assay. Furthermore, the direct binding site of EB to UBE2D3 was identified using high‐resolution mass spectrometry and confirmed by experiments. Taken together, EB ameliorates periodontitis by targeting UBE2D3 to suppress the ubiquitination degradation of IκBα, leading to inactivation of nuclear transcription factor‐κB signaling pathway. And this was confirmed by siRNA‐mediated gene knockdown in inflammatory macrophages. Our results suggested that EB may be a new kind of UBE2D3 inhibitor and may become a promising therapeutic agent for anti‐periodontitis. |
| format | Article |
| id | doaj-art-904f5d6b8d164bd9a49607b6cd20fcf9 |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-904f5d6b8d164bd9a49607b6cd20fcf92025-01-20T01:45:44ZengWileyMedComm2688-26632025-01-0161n/an/a10.1002/mco2.70034Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3Wenhua Kuang0Ruishen Zhuge1Ping Song2Letai Yi3Shujie Zhang4Ying Zhang5Yin Kwan Wong6Ruixing Chen7Junzhe Zhang8Yuanbo Wang9Dandan Liu10Zipeng Gong11Peili Wang12Xiangying Ouyang13Jigang Wang14Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics Guizhou Medical University Guiyang ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaDepartment of Periodontology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology Beijing ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology Shenzhen ChinaAbstract Periodontitis is a chronic periodontal inflammatory disease caused by periodontal pathogens commonly seen in adults. Eupalinolide B (EB) is a sesquiterpenoid natural product extracted from Eupatorium lindleyanum and has been reported as a potential drug for cancers and immune disorders. Here, we explored the ameliorative effects and underlying molecular mechanism of EB on periodontitis for the first time. We demonstrated that EB ameliorates periodontal inflammation and alveolar bone resorption with a ligated periodontitis mouse model. In addition, the impact of EB on macrophages inflammation was examined in the Raw264.7 cell line. We identified ubiquitin‐conjugating enzyme, UBE2D3, as the direct covalent binding protein targets of EB by using a chemoproteomic method based on activity‐based protein profiling, biolayer interferometry method, and cellular thermal shift assay. Furthermore, the direct binding site of EB to UBE2D3 was identified using high‐resolution mass spectrometry and confirmed by experiments. Taken together, EB ameliorates periodontitis by targeting UBE2D3 to suppress the ubiquitination degradation of IκBα, leading to inactivation of nuclear transcription factor‐κB signaling pathway. And this was confirmed by siRNA‐mediated gene knockdown in inflammatory macrophages. Our results suggested that EB may be a new kind of UBE2D3 inhibitor and may become a promising therapeutic agent for anti‐periodontitis.https://doi.org/10.1002/mco2.70034chemical biologydrug targetsnatural productproteomicstarget identification |
| spellingShingle | Wenhua Kuang Ruishen Zhuge Ping Song Letai Yi Shujie Zhang Ying Zhang Yin Kwan Wong Ruixing Chen Junzhe Zhang Yuanbo Wang Dandan Liu Zipeng Gong Peili Wang Xiangying Ouyang Jigang Wang Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3 MedComm chemical biology drug targets natural product proteomics target identification |
| title | Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3 |
| title_full | Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3 |
| title_fullStr | Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3 |
| title_full_unstemmed | Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3 |
| title_short | Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3 |
| title_sort | eupalinolide b inhibits periodontitis development by targeting ubiquitin conjugating enzyme ube2d3 |
| topic | chemical biology drug targets natural product proteomics target identification |
| url | https://doi.org/10.1002/mco2.70034 |
| work_keys_str_mv | AT wenhuakuang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT ruishenzhuge eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT pingsong eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT letaiyi eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT shujiezhang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT yingzhang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT yinkwanwong eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT ruixingchen eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT junzhezhang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT yuanbowang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT dandanliu eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT zipenggong eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT peiliwang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT xiangyingouyang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 AT jigangwang eupalinolidebinhibitsperiodontitisdevelopmentbytargetingubiquitinconjugatingenzymeube2d3 |