The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway
(+)-Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine sponge <i>Aplysina aerophoba</i> that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells, inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/10/605 |
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| author | Isabel Vidal Laura Castilla Ana Dácil Marrero Inés Bravo-Ruiz Manuel Bernal Inmaculada Manrique Ana R. Quesada Miguel Ángel Medina Beatriz Martínez-Poveda |
| author_facet | Isabel Vidal Laura Castilla Ana Dácil Marrero Inés Bravo-Ruiz Manuel Bernal Inmaculada Manrique Ana R. Quesada Miguel Ángel Medina Beatriz Martínez-Poveda |
| author_sort | Isabel Vidal |
| collection | DOAJ |
| description | (+)-Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine sponge <i>Aplysina aerophoba</i> that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells, inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell types, among other reported activities. In addition to the aforementioned effects, the anti-inflammatory potential of this natural compound was explored in previous work of our laboratory, but the mechanism of action underlying this effect was not described. In this work, we delve into the anti-inflammatory effect of Apl-1 in the context of vascular endothelial cells in vitro, providing new data regarding the molecular mechanism underlying this activity. The characterization of the mechanism of action points to an inhibitory effect of Apl-1 on the NF-κB pathway, one of the main axes involved in endothelial response during inflammatory events. Our results show that Apl-1 can inhibit the expression of pro-inflammatory genes in tumor necrosis factor alpha (TNF-α)- and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), targeting the nuclear factor kappa B subunit (NF-κB) pathway through a mechanism of action involving the inhibition of I kappa B kinase (IKK) complex phosphorylation and RelA/p65 nuclear import. In addition, Apl-1 prevented the phosphorylation of Akt induced by TNF-α in HUVECs, probably supporting the inhibitory effect of this compound in the NF-κB pathway. Experimental evidence reported in this work opens the door to the potential pharmacological use of this compound as an anti-inflammatory agent in diseases that course with a pathological endothelial response to inflammation, such as atherosclerosis. |
| first_indexed | 2024-03-09T19:54:07Z |
| format | Article |
| id | doaj.art-705f6999d5d2466495144f508d22baf0 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T19:54:07Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-705f6999d5d2466495144f508d22baf02023-11-24T01:01:00ZengMDPI AGMarine Drugs1660-33972022-09-01201060510.3390/md20100605The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB PathwayIsabel Vidal0Laura Castilla1Ana Dácil Marrero2Inés Bravo-Ruiz3Manuel Bernal4Inmaculada Manrique5Ana R. Quesada6Miguel Ángel Medina7Beatriz Martínez-Poveda8Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, SpainDepartamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Andalucía Tech, 29071 Málaga, Spain(+)-Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine sponge <i>Aplysina aerophoba</i> that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells, inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell types, among other reported activities. In addition to the aforementioned effects, the anti-inflammatory potential of this natural compound was explored in previous work of our laboratory, but the mechanism of action underlying this effect was not described. In this work, we delve into the anti-inflammatory effect of Apl-1 in the context of vascular endothelial cells in vitro, providing new data regarding the molecular mechanism underlying this activity. The characterization of the mechanism of action points to an inhibitory effect of Apl-1 on the NF-κB pathway, one of the main axes involved in endothelial response during inflammatory events. Our results show that Apl-1 can inhibit the expression of pro-inflammatory genes in tumor necrosis factor alpha (TNF-α)- and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), targeting the nuclear factor kappa B subunit (NF-κB) pathway through a mechanism of action involving the inhibition of I kappa B kinase (IKK) complex phosphorylation and RelA/p65 nuclear import. In addition, Apl-1 prevented the phosphorylation of Akt induced by TNF-α in HUVECs, probably supporting the inhibitory effect of this compound in the NF-κB pathway. Experimental evidence reported in this work opens the door to the potential pharmacological use of this compound as an anti-inflammatory agent in diseases that course with a pathological endothelial response to inflammation, such as atherosclerosis.https://www.mdpi.com/1660-3397/20/10/605aeroplysinin-1marine-sponge-derived metabolitesendothelial cellsinflammationNF-κB pathwayPI3K/Akt pathway |
| spellingShingle | Isabel Vidal Laura Castilla Ana Dácil Marrero Inés Bravo-Ruiz Manuel Bernal Inmaculada Manrique Ana R. Quesada Miguel Ángel Medina Beatriz Martínez-Poveda The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway Marine Drugs aeroplysinin-1 marine-sponge-derived metabolites endothelial cells inflammation NF-κB pathway PI3K/Akt pathway |
| title | The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway |
| title_full | The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway |
| title_fullStr | The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway |
| title_full_unstemmed | The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway |
| title_short | The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway |
| title_sort | sponge derived brominated compound aeroplysinin 1 impairs the endothelial inflammatory response through inhibition of the nf κb pathway |
| topic | aeroplysinin-1 marine-sponge-derived metabolites endothelial cells inflammation NF-κB pathway PI3K/Akt pathway |
| url | https://www.mdpi.com/1660-3397/20/10/605 |
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