5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation
IntroductionAcute lung injury (ALI) induced by lipopolysaccharide (LPS) is a significant medical condition characterized by severe pulmonary inflammation and tissue damage. NLRP3 inflammasome-driven inflammation is essential in ALI pathogenesis, inspiring novel therapeutic strategies that focus on N...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1522146/full |
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| author | Jinque Luo Jinque Luo Xin Li Xin Li Li Zhang Li Zhang Meijing Deng Jieyang Zhao Jinghuan Zhang Wenyu Tang Qinghua Guo Ling Wang |
| author_facet | Jinque Luo Jinque Luo Xin Li Xin Li Li Zhang Li Zhang Meijing Deng Jieyang Zhao Jinghuan Zhang Wenyu Tang Qinghua Guo Ling Wang |
| author_sort | Jinque Luo |
| collection | DOAJ |
| description | IntroductionAcute lung injury (ALI) induced by lipopolysaccharide (LPS) is a significant medical condition characterized by severe pulmonary inflammation and tissue damage. NLRP3 inflammasome-driven inflammation is essential in ALI pathogenesis, inspiring novel therapeutic strategies that focus on NLRP3 and inflammation. In this study, we investigated the therapeutic potential of 5-deoxy-rutaecarpine (5-DR), a rutaecarpine derivative, in attenuating LPS-induced ALI.MethodsIn this study, we evaluated the effects of 5-DR treatment in mice exposed to LPS, lung tissues, bronchoalveolar lavage fluid, and serum were collected for analysis. LPS-stimulated J774A.1 mouse macrophages were used to further investigate the anti-inflammatory effects of 5-DR in vitro. Various techniques including histopathology, Western blotting, and luciferase reporter assay were employed.Results5-DR treatment significantly reduced lung edema, inflammatory cell infiltration in mice with LPS burden, and reduced the levels of inflammatory mediators like interleukin-1β in the mice and in LPS-stimulated J774A.1 mouse macrophages. Further western blotting analysis showed 5-DR decreased the levels of NLRP3, cleaved caspase-1, and mature IL-1β in mice and J774A.1 cells exposed to LPS. Additionally, NF-κB pathway activation significantly diminished the inhibition of the NLRP3 inflammasome by 5-DR.DiscussionOur findings highlight the therapeutic potential of 5-DR as a promising candidate for treating LPS-induced ALI, offering insights into its underlying mechanism that targets NLRP3 inflammasome-mediated inflammation. |
| format | Article |
| id | doaj-art-0bad7d819bb94fc3956f522da1d8f822 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-0bad7d819bb94fc3956f522da1d8f8222025-01-28T06:41:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011610.3389/fphar.2025.152214615221465-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammationJinque Luo0Jinque Luo1Xin Li2Xin Li3Li Zhang4Li Zhang5Meijing Deng6Jieyang Zhao7Jinghuan Zhang8Wenyu Tang9Qinghua Guo10Ling Wang11Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaHunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaHunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaHunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaThe National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Science, Hunan Normal University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaDepartment of Emergency, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, Changsha, Hunan, ChinaIntroductionAcute lung injury (ALI) induced by lipopolysaccharide (LPS) is a significant medical condition characterized by severe pulmonary inflammation and tissue damage. NLRP3 inflammasome-driven inflammation is essential in ALI pathogenesis, inspiring novel therapeutic strategies that focus on NLRP3 and inflammation. In this study, we investigated the therapeutic potential of 5-deoxy-rutaecarpine (5-DR), a rutaecarpine derivative, in attenuating LPS-induced ALI.MethodsIn this study, we evaluated the effects of 5-DR treatment in mice exposed to LPS, lung tissues, bronchoalveolar lavage fluid, and serum were collected for analysis. LPS-stimulated J774A.1 mouse macrophages were used to further investigate the anti-inflammatory effects of 5-DR in vitro. Various techniques including histopathology, Western blotting, and luciferase reporter assay were employed.Results5-DR treatment significantly reduced lung edema, inflammatory cell infiltration in mice with LPS burden, and reduced the levels of inflammatory mediators like interleukin-1β in the mice and in LPS-stimulated J774A.1 mouse macrophages. Further western blotting analysis showed 5-DR decreased the levels of NLRP3, cleaved caspase-1, and mature IL-1β in mice and J774A.1 cells exposed to LPS. Additionally, NF-κB pathway activation significantly diminished the inhibition of the NLRP3 inflammasome by 5-DR.DiscussionOur findings highlight the therapeutic potential of 5-DR as a promising candidate for treating LPS-induced ALI, offering insights into its underlying mechanism that targets NLRP3 inflammasome-mediated inflammation.https://www.frontiersin.org/articles/10.3389/fphar.2025.1522146/full5-DRacute lung injurylipopolysaccharideinflammationNLRP3 inflammasome |
| spellingShingle | Jinque Luo Jinque Luo Xin Li Xin Li Li Zhang Li Zhang Meijing Deng Jieyang Zhao Jinghuan Zhang Wenyu Tang Qinghua Guo Ling Wang 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation Frontiers in Pharmacology 5-DR acute lung injury lipopolysaccharide inflammation NLRP3 inflammasome |
| title | 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation |
| title_full | 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation |
| title_fullStr | 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation |
| title_full_unstemmed | 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation |
| title_short | 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation |
| title_sort | 5 deoxy rutaecarpine protects against lps induced acute lung injury via inhibiting nlrp3 inflammasome related inflammation |
| topic | 5-DR acute lung injury lipopolysaccharide inflammation NLRP3 inflammasome |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1522146/full |
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