The ocean as a source of new anti-inflammatory and anti-pruritic molecules

Detalhes bibliográficos
Autor(a) principal: Martins , M. S.
Data de Publicação: 2023
Outros Autores: Long , S., Pinto , M. M. M., Almeida , I. F., Cruz , M. T., Sousa, E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.48797/sl.2023.85
Resumo: Background: Pruritus, the most common symptom of skin diseases, is considered a chronic condition when experienced for more than six weeks. Although the etiology of the symptom remains elusive, chronic pruritus has been associated with neurokinin 1 receptor (NK1R) and its agonist substance P [1]. Since pruritus and inflammation often go together, the development of compounds with dual activity, specifically anti-inflammatory and anti-pruritic, is an upcoming strategy [1,2]. Objective: The present work aimed the discovery of new molecules inspired in models from the sea, a source of unique chemical structures with anti-pruritic and anti-inflammatory activities. Methods: Seventy marine-inspired compounds were tested in silico regarding their binding affinity to NK1R and their pharmacokinetic properties evaluated using SwissADME software. In vitro molecules’ cytotoxicity was evaluated in cells representative of the skin constitution, namely keratinocytes (HaCaT), macrophages (Raw 264.7), and fibroblasts (3T3). The anti-inflammatory properties were investigated in macrophages, by evaluating nitric oxide synthase (iNOS) protein levels (Western blot analysis), nitric oxide (NO) production (Griess assay) and NO scavenging potential using an in chimico assay. Results: The tested compounds demonstrated a high binding affinity for NK1R in silico and no relevant cytotoxicity in vitro. Some compounds were able to reduce inflammation through the decrease of the pro-inflammatory mediator NO, not because of their NO scavenging potential, but by decreasing iNOS protein levels, thus suggesting the blockade of pro-inflammatory signaling pathways upstream iNOS synthesis, namely the transcription factor NF-kB. Importantly, most tested marine-inspired compounds presented MW up to 500 and log P in the range 2.40-5.76 which favours good skin permeation. Conclusions: The ocean is a potential source of anti-inflammatory compounds and NK1R antagonists for the treatment of skin conditions associated with pruritus and inflame mation.
id RCAP_811a195ee32945b6d5767af6d88fea2d
oai_identifier_str oai:publicacoes.cespu.pt:article/85
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling The ocean as a source of new anti-inflammatory and anti-pruritic moleculesPosterBackground: Pruritus, the most common symptom of skin diseases, is considered a chronic condition when experienced for more than six weeks. Although the etiology of the symptom remains elusive, chronic pruritus has been associated with neurokinin 1 receptor (NK1R) and its agonist substance P [1]. Since pruritus and inflammation often go together, the development of compounds with dual activity, specifically anti-inflammatory and anti-pruritic, is an upcoming strategy [1,2]. Objective: The present work aimed the discovery of new molecules inspired in models from the sea, a source of unique chemical structures with anti-pruritic and anti-inflammatory activities. Methods: Seventy marine-inspired compounds were tested in silico regarding their binding affinity to NK1R and their pharmacokinetic properties evaluated using SwissADME software. In vitro molecules’ cytotoxicity was evaluated in cells representative of the skin constitution, namely keratinocytes (HaCaT), macrophages (Raw 264.7), and fibroblasts (3T3). The anti-inflammatory properties were investigated in macrophages, by evaluating nitric oxide synthase (iNOS) protein levels (Western blot analysis), nitric oxide (NO) production (Griess assay) and NO scavenging potential using an in chimico assay. Results: The tested compounds demonstrated a high binding affinity for NK1R in silico and no relevant cytotoxicity in vitro. Some compounds were able to reduce inflammation through the decrease of the pro-inflammatory mediator NO, not because of their NO scavenging potential, but by decreasing iNOS protein levels, thus suggesting the blockade of pro-inflammatory signaling pathways upstream iNOS synthesis, namely the transcription factor NF-kB. Importantly, most tested marine-inspired compounds presented MW up to 500 and log P in the range 2.40-5.76 which favours good skin permeation. Conclusions: The ocean is a potential source of anti-inflammatory compounds and NK1R antagonists for the treatment of skin conditions associated with pruritus and inflame mation.IUCS-CESPU Publishing2023-04-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.48797/sl.2023.85https://doi.org/10.48797/sl.2023.85Scientific Letters; Vol. 1 No. Sup 1 (2023)2795-5117reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPenghttps://publicacoes.cespu.pt/index.php/sl/article/view/85https://publicacoes.cespu.pt/index.php/sl/article/view/85/79Copyright (c) 2023 M. S. Martins , S. Long , M. M. M. Pinto , I. F. Almeida , M. T. Cruz , E. Sousainfo:eu-repo/semantics/openAccessMartins , M. S.Long , S.Pinto , M. M. M.Almeida , I. F.Cruz , M. T.Sousa, E.2023-04-29T08:46:11Zoai:publicacoes.cespu.pt:article/85Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:50:23.894010Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The ocean as a source of new anti-inflammatory and anti-pruritic molecules
title The ocean as a source of new anti-inflammatory and anti-pruritic molecules
spellingShingle The ocean as a source of new anti-inflammatory and anti-pruritic molecules
Martins , M. S.
Poster
title_short The ocean as a source of new anti-inflammatory and anti-pruritic molecules
title_full The ocean as a source of new anti-inflammatory and anti-pruritic molecules
title_fullStr The ocean as a source of new anti-inflammatory and anti-pruritic molecules
title_full_unstemmed The ocean as a source of new anti-inflammatory and anti-pruritic molecules
title_sort The ocean as a source of new anti-inflammatory and anti-pruritic molecules
author Martins , M. S.
author_facet Martins , M. S.
Long , S.
Pinto , M. M. M.
Almeida , I. F.
Cruz , M. T.
Sousa, E.
author_role author
author2 Long , S.
Pinto , M. M. M.
Almeida , I. F.
Cruz , M. T.
Sousa, E.
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Martins , M. S.
Long , S.
Pinto , M. M. M.
Almeida , I. F.
Cruz , M. T.
Sousa, E.
dc.subject.por.fl_str_mv Poster
topic Poster
description Background: Pruritus, the most common symptom of skin diseases, is considered a chronic condition when experienced for more than six weeks. Although the etiology of the symptom remains elusive, chronic pruritus has been associated with neurokinin 1 receptor (NK1R) and its agonist substance P [1]. Since pruritus and inflammation often go together, the development of compounds with dual activity, specifically anti-inflammatory and anti-pruritic, is an upcoming strategy [1,2]. Objective: The present work aimed the discovery of new molecules inspired in models from the sea, a source of unique chemical structures with anti-pruritic and anti-inflammatory activities. Methods: Seventy marine-inspired compounds were tested in silico regarding their binding affinity to NK1R and their pharmacokinetic properties evaluated using SwissADME software. In vitro molecules’ cytotoxicity was evaluated in cells representative of the skin constitution, namely keratinocytes (HaCaT), macrophages (Raw 264.7), and fibroblasts (3T3). The anti-inflammatory properties were investigated in macrophages, by evaluating nitric oxide synthase (iNOS) protein levels (Western blot analysis), nitric oxide (NO) production (Griess assay) and NO scavenging potential using an in chimico assay. Results: The tested compounds demonstrated a high binding affinity for NK1R in silico and no relevant cytotoxicity in vitro. Some compounds were able to reduce inflammation through the decrease of the pro-inflammatory mediator NO, not because of their NO scavenging potential, but by decreasing iNOS protein levels, thus suggesting the blockade of pro-inflammatory signaling pathways upstream iNOS synthesis, namely the transcription factor NF-kB. Importantly, most tested marine-inspired compounds presented MW up to 500 and log P in the range 2.40-5.76 which favours good skin permeation. Conclusions: The ocean is a potential source of anti-inflammatory compounds and NK1R antagonists for the treatment of skin conditions associated with pruritus and inflame mation.
publishDate 2023
dc.date.none.fl_str_mv 2023-04-21
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.48797/sl.2023.85
https://doi.org/10.48797/sl.2023.85
url https://doi.org/10.48797/sl.2023.85
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://publicacoes.cespu.pt/index.php/sl/article/view/85
https://publicacoes.cespu.pt/index.php/sl/article/view/85/79
dc.rights.driver.fl_str_mv Copyright (c) 2023 M. S. Martins , S. Long , M. M. M. Pinto , I. F. Almeida , M. T. Cruz , E. Sousa
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2023 M. S. Martins , S. Long , M. M. M. Pinto , I. F. Almeida , M. T. Cruz , E. Sousa
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv IUCS-CESPU Publishing
publisher.none.fl_str_mv IUCS-CESPU Publishing
dc.source.none.fl_str_mv Scientific Letters; Vol. 1 No. Sup 1 (2023)
2795-5117
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799131583770263552