The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor
Inflammation plays a central role in various pathological conditions, necessitating the search for safer and more effective anti-inflammatory agents. This study investigates the anti-inflammatory activity of caulerpin, a bisindolic alkaloid isolated from <i>Caulerpa racemosa</i>. In vitr...
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MDPI AG
2025-05-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/6/232 |
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| author | Jônatas Sousa Pires dos Santos Dahara Keyse Carvalho Silva Vanessa da Silva Oliveira Sergio Santos Silva Junior Edivaldo dos Santos Rodrigues Claudia Valeria Campos de Souza Sabrina Teixeira Martinez Osvaldo Andrade Santos-Filho Cássio Santana Meira Milena Botelho Pereira Soares |
| author_facet | Jônatas Sousa Pires dos Santos Dahara Keyse Carvalho Silva Vanessa da Silva Oliveira Sergio Santos Silva Junior Edivaldo dos Santos Rodrigues Claudia Valeria Campos de Souza Sabrina Teixeira Martinez Osvaldo Andrade Santos-Filho Cássio Santana Meira Milena Botelho Pereira Soares |
| author_sort | Jônatas Sousa Pires dos Santos |
| collection | DOAJ |
| description | Inflammation plays a central role in various pathological conditions, necessitating the search for safer and more effective anti-inflammatory agents. This study investigates the anti-inflammatory activity of caulerpin, a bisindolic alkaloid isolated from <i>Caulerpa racemosa</i>. In vitro assays demonstrated that caulerpin significantly reduced nitric oxide, TNF-α, IL-6, and IL-12 levels in macrophages stimulated with LPS + IFN-γ, without affecting cell viability. In silico toxicity predictions using Protox 3.0 reinforce a favorable safety profile of caulerpin. Molecular docking and molecular dynamics simulations revealed its high-affinity binding to the glucocorticoid receptor ligand-binding domain (GR-LBD), suggesting a mechanism of action similar to dexamethasone. The involvement of the glucocorticoid receptor was confirmed by the partial reversal of caulerpin’s effects upon RU486 treatment. In vivo, caulerpin exhibited a favorable safety profile, with no signs of acute toxicity at an oral dose of 100 mg/kg. Moreover, in a mouse model of endotoxic shock, caulerpin administration significantly improved survival rates in a dose-dependent manner, providing complete protection at 4 mg/kg. These findings highlight caulerpin as a promising candidate for the development of novel anti-inflammatory therapies. Further studies are warranted to explore its pharmacokinetics, optimize its structure, and evaluate its efficacy in chronic inflammatory diseases. |
| format | Article |
| id | doaj-art-7e139deafbbd4bd88c8b3fab7ea31100 |
| institution | DOAJ |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-7e139deafbbd4bd88c8b3fab7ea311002025-08-20T03:16:33ZengMDPI AGMarine Drugs1660-33972025-05-0123623210.3390/md23060232The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid ReceptorJônatas Sousa Pires dos Santos0Dahara Keyse Carvalho Silva1Vanessa da Silva Oliveira2Sergio Santos Silva Junior3Edivaldo dos Santos Rodrigues4Claudia Valeria Campos de Souza5Sabrina Teixeira Martinez6Osvaldo Andrade Santos-Filho7Cássio Santana Meira8Milena Botelho Pereira Soares9Department of Life Sciences, State University of Bahia (UNEB), Salvador 40020-000, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Salvador 40296-710, BrazilDepartment of Life Sciences, State University of Bahia (UNEB), Salvador 40020-000, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Salvador 40296-710, BrazilLaboratory of Molecular Modeling and Computational Structural Biology, Walter Mors Natural Products Research Institute, Health Sciences Center, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-599, BrazilLaboratory of Molecular Modeling and Computational Structural Biology, Walter Mors Natural Products Research Institute, Health Sciences Center, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-599, BrazilInstitute of Innovation in Advanced Health Systems (ISI SAS), University SENAI/CIMATEC, Salvador 41650-010, BrazilLaboratory of Molecular Modeling and Computational Structural Biology, Walter Mors Natural Products Research Institute, Health Sciences Center, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-599, BrazilDepartment of Life Sciences, State University of Bahia (UNEB), Salvador 40020-000, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Salvador 40296-710, BrazilInflammation plays a central role in various pathological conditions, necessitating the search for safer and more effective anti-inflammatory agents. This study investigates the anti-inflammatory activity of caulerpin, a bisindolic alkaloid isolated from <i>Caulerpa racemosa</i>. In vitro assays demonstrated that caulerpin significantly reduced nitric oxide, TNF-α, IL-6, and IL-12 levels in macrophages stimulated with LPS + IFN-γ, without affecting cell viability. In silico toxicity predictions using Protox 3.0 reinforce a favorable safety profile of caulerpin. Molecular docking and molecular dynamics simulations revealed its high-affinity binding to the glucocorticoid receptor ligand-binding domain (GR-LBD), suggesting a mechanism of action similar to dexamethasone. The involvement of the glucocorticoid receptor was confirmed by the partial reversal of caulerpin’s effects upon RU486 treatment. In vivo, caulerpin exhibited a favorable safety profile, with no signs of acute toxicity at an oral dose of 100 mg/kg. Moreover, in a mouse model of endotoxic shock, caulerpin administration significantly improved survival rates in a dose-dependent manner, providing complete protection at 4 mg/kg. These findings highlight caulerpin as a promising candidate for the development of novel anti-inflammatory therapies. Further studies are warranted to explore its pharmacokinetics, optimize its structure, and evaluate its efficacy in chronic inflammatory diseases.https://www.mdpi.com/1660-3397/23/6/232caulerpinglucocorticoid receptormacrophagesanti-inflammatory activity |
| spellingShingle | Jônatas Sousa Pires dos Santos Dahara Keyse Carvalho Silva Vanessa da Silva Oliveira Sergio Santos Silva Junior Edivaldo dos Santos Rodrigues Claudia Valeria Campos de Souza Sabrina Teixeira Martinez Osvaldo Andrade Santos-Filho Cássio Santana Meira Milena Botelho Pereira Soares The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor Marine Drugs caulerpin glucocorticoid receptor macrophages anti-inflammatory activity |
| title | The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor |
| title_full | The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor |
| title_fullStr | The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor |
| title_full_unstemmed | The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor |
| title_short | The Alkaloid Caulerpin Exhibits Potent and Selective Anti-Inflammatory Activity Through Interaction with the Glucocorticoid Receptor |
| title_sort | alkaloid caulerpin exhibits potent and selective anti inflammatory activity through interaction with the glucocorticoid receptor |
| topic | caulerpin glucocorticoid receptor macrophages anti-inflammatory activity |
| url | https://www.mdpi.com/1660-3397/23/6/232 |
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