Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro
Chrysophanol (Chr) is the main monomer isolated from Rheum rhabarbarum. This study aimed to identify the potential in vitro and in vivo cytoprotective effects of Chr on lipopolysaccharide (LPS)-triggered acute lung injury (ALI). We used an ALI-murine model and constructed an inflammatory macrophage...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2020.623866/full |
| _version_ | 1818930772115980288 |
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| author | Quan Wen Quan Wen Ngaikeung Lau Huandi Weng Peng Ye Shaohui Du Chun Li Jianping Lv Hui Li |
| author_facet | Quan Wen Quan Wen Ngaikeung Lau Huandi Weng Peng Ye Shaohui Du Chun Li Jianping Lv Hui Li |
| author_sort | Quan Wen |
| collection | DOAJ |
| description | Chrysophanol (Chr) is the main monomer isolated from Rheum rhabarbarum. This study aimed to identify the potential in vitro and in vivo cytoprotective effects of Chr on lipopolysaccharide (LPS)-triggered acute lung injury (ALI). We used an ALI-murine model and constructed an inflammatory macrophage in vitro cell model to determine the cellular mechanisms involved in Chr-mediated activity. To observe the vital role of histone deacetylase 3 (HDAC3) in abolishing inflammation action, HDAC3 was downregulated using small interfering RNA. Analysis of the expression of nuclear transcription factor-kappa B p65 (NF-κB p65) and molecules of its downstream signaling pathway were assessed in vitro and in lung tissue samples using the mouse model. Concentrations of tumor necrosis factor-α, interleukin-1β, high mobility group protein 1 (HMGB1), and interleukin-16 in supernatants and the bronchoalveolar lavage fluid were measured using enzyme-linked immunosorbent assay. A reporter gene assay measured HMGB1 activity, and NF-κB p65 and HMGB1 intracellular localization was determined by immunofluorescence detection on histological lung samples from Chr-treated mice. The protein interactions between HMGB1, HDAC3, and NF-κB p65 were tested by co-immunoprecipitation. Chr treatment relieved LPS-induced lung lesions. Chr also enhanced superoxide dismutase levels in ALI mice. Chr reduced the LPS-induced protein expression of NF-κB and its related pathway molecules in both in vivo and in vitro models. Moreover, Chr downregulated LPS-enhanced HMGB1 expression, acetylation, and nuclear nucleocytoplasmic translocation. However, HDAC3 knockdown substantially reduced Chr-mediated HDAC3/NF-κB expression.Furthermore, Chr enhanced HMGB1/HDAC3/NF-κB p65 complex interaction, whereas HDAC3 knockdown reduced Chr-mediated HMGB1/HDAC3/NF-κB p65 formation. This study showed that the protective effects induced by Chr were associated with the regulation of the HMGB1/NF-κB pathway via HDAC3. |
| first_indexed | 2024-12-20T04:06:00Z |
| format | Article |
| id | doaj.art-96620deed6934dcabf73bfe21f70b5f5 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-20T04:06:00Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-96620deed6934dcabf73bfe21f70b5f52022-12-21T19:54:02ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-01-01810.3389/fbioe.2020.623866623866Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitroQuan Wen0Quan Wen1Ngaikeung Lau2Huandi Weng3Peng Ye4Shaohui Du5Chun Li6Jianping Lv7Hui Li8Guangdong-HongKong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaGuangdong-HongKong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaShenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Nursing Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Neurosurgery, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaChrysophanol (Chr) is the main monomer isolated from Rheum rhabarbarum. This study aimed to identify the potential in vitro and in vivo cytoprotective effects of Chr on lipopolysaccharide (LPS)-triggered acute lung injury (ALI). We used an ALI-murine model and constructed an inflammatory macrophage in vitro cell model to determine the cellular mechanisms involved in Chr-mediated activity. To observe the vital role of histone deacetylase 3 (HDAC3) in abolishing inflammation action, HDAC3 was downregulated using small interfering RNA. Analysis of the expression of nuclear transcription factor-kappa B p65 (NF-κB p65) and molecules of its downstream signaling pathway were assessed in vitro and in lung tissue samples using the mouse model. Concentrations of tumor necrosis factor-α, interleukin-1β, high mobility group protein 1 (HMGB1), and interleukin-16 in supernatants and the bronchoalveolar lavage fluid were measured using enzyme-linked immunosorbent assay. A reporter gene assay measured HMGB1 activity, and NF-κB p65 and HMGB1 intracellular localization was determined by immunofluorescence detection on histological lung samples from Chr-treated mice. The protein interactions between HMGB1, HDAC3, and NF-κB p65 were tested by co-immunoprecipitation. Chr treatment relieved LPS-induced lung lesions. Chr also enhanced superoxide dismutase levels in ALI mice. Chr reduced the LPS-induced protein expression of NF-κB and its related pathway molecules in both in vivo and in vitro models. Moreover, Chr downregulated LPS-enhanced HMGB1 expression, acetylation, and nuclear nucleocytoplasmic translocation. However, HDAC3 knockdown substantially reduced Chr-mediated HDAC3/NF-κB expression.Furthermore, Chr enhanced HMGB1/HDAC3/NF-κB p65 complex interaction, whereas HDAC3 knockdown reduced Chr-mediated HMGB1/HDAC3/NF-κB p65 formation. This study showed that the protective effects induced by Chr were associated with the regulation of the HMGB1/NF-κB pathway via HDAC3.https://www.frontiersin.org/articles/10.3389/fbioe.2020.623866/fullchrysophanolsepsisHMGB1HDAC3NF-κB |
| spellingShingle | Quan Wen Quan Wen Ngaikeung Lau Huandi Weng Peng Ye Shaohui Du Chun Li Jianping Lv Hui Li Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro Frontiers in Bioengineering and Biotechnology chrysophanol sepsis HMGB1 HDAC3 NF-κB |
| title | Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro |
| title_full | Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro |
| title_fullStr | Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro |
| title_full_unstemmed | Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro |
| title_short | Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro |
| title_sort | chrysophanol exerts anti inflammatory activity by targeting histone deacetylase 3 through the high mobility group protein 1 nuclear transcription factor kappa b signaling pathway in vivo and in vitro |
| topic | chrysophanol sepsis HMGB1 HDAC3 NF-κB |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2020.623866/full |
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