Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/106704 https://doi.org/10.1038/s41598-020-64032-1 |
Resumo: | Mint species are widely used in traditional and conventional medicine as topical analgesics for osteoarthritic pain and for disorders of the gastrointestinal and respiratory tracts which are all associated with chronic inflammation. To identify the structural determinants of anti-inflammatory activity and potency which are required for chemical optimization towards development of new anti-inflammatory drugs, a selected group of monoterpenes especially abundant in mint species was screened by measuring bacterial lipopolysacharide (LPS)-induced nitric oxide (NO) production in murine macrophages. Nine compounds significantly decreased LPS-induced NO production by more than 30%. IC50 values were calculated showing that the order of potency is: (S)-(+)-carvone > (R)-(-)-carvone > (+)-dihydrocarveol > (S)-8-hydroxycarvotanacetone > (R)-8-hydroxycarvotanacetone > (+)-dihydrocarvone > (-)-carveol > (-)-dihydrocarveol > (S)-(-)-pulegone. Considering the carbon numbering relative to the common precursor, limonene, the presence of an oxygenated group at C6 conjugated to a double bond at C1 and an isopropenyl group and S configuration at C4 are the major chemical features relevant for activity and potency. The most potent compound, (S)-(+)-carvone, significantly decreased the expression of NOS2 and IL-1β in macrophages and in a cell model of osteoarthritis using primary human chondrocytes. (S)-(+)-carvone may be efficient in halting inflammation-related diseases, like osteoarthritis. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
spelling |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activityAnimalsChondrocytesHumansLipopolysaccharidesMiceNitric OxideNitric Oxide Synthase Type IIOsteoarthritisRAW 264.7 CellsStructure-Activity RelationshipAnti-Inflammatory AgentsLimoneneModels, BiologicalMint species are widely used in traditional and conventional medicine as topical analgesics for osteoarthritic pain and for disorders of the gastrointestinal and respiratory tracts which are all associated with chronic inflammation. To identify the structural determinants of anti-inflammatory activity and potency which are required for chemical optimization towards development of new anti-inflammatory drugs, a selected group of monoterpenes especially abundant in mint species was screened by measuring bacterial lipopolysacharide (LPS)-induced nitric oxide (NO) production in murine macrophages. Nine compounds significantly decreased LPS-induced NO production by more than 30%. IC50 values were calculated showing that the order of potency is: (S)-(+)-carvone > (R)-(-)-carvone > (+)-dihydrocarveol > (S)-8-hydroxycarvotanacetone > (R)-8-hydroxycarvotanacetone > (+)-dihydrocarvone > (-)-carveol > (-)-dihydrocarveol > (S)-(-)-pulegone. Considering the carbon numbering relative to the common precursor, limonene, the presence of an oxygenated group at C6 conjugated to a double bond at C1 and an isopropenyl group and S configuration at C4 are the major chemical features relevant for activity and potency. The most potent compound, (S)-(+)-carvone, significantly decreased the expression of NOS2 and IL-1β in macrophages and in a cell model of osteoarthritis using primary human chondrocytes. (S)-(+)-carvone may be efficient in halting inflammation-related diseases, like osteoarthritis.Springer Nature2020-04-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106704http://hdl.handle.net/10316/106704https://doi.org/10.1038/s41598-020-64032-1eng2045-2322Sousa, CátiaLeitão, Alcino JorgeNeves, Bruno MiguelJudas, FernandoCavaleiro, CarlosMendes, Alexandrina F.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-18T08:23:19Zoai:estudogeral.uc.pt:10316/106704Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:07.254206Repositório 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 |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity |
title |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity |
spellingShingle |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity Sousa, Cátia Animals Chondrocytes Humans Lipopolysaccharides Mice Nitric Oxide Nitric Oxide Synthase Type II Osteoarthritis RAW 264.7 Cells Structure-Activity Relationship Anti-Inflammatory Agents Limonene Models, Biological |
title_short |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity |
title_full |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity |
title_fullStr |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity |
title_full_unstemmed |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity |
title_sort |
Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity |
author |
Sousa, Cátia |
author_facet |
Sousa, Cátia Leitão, Alcino Jorge Neves, Bruno Miguel Judas, Fernando Cavaleiro, Carlos Mendes, Alexandrina F. |
author_role |
author |
author2 |
Leitão, Alcino Jorge Neves, Bruno Miguel Judas, Fernando Cavaleiro, Carlos Mendes, Alexandrina F. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Sousa, Cátia Leitão, Alcino Jorge Neves, Bruno Miguel Judas, Fernando Cavaleiro, Carlos Mendes, Alexandrina F. |
dc.subject.por.fl_str_mv |
Animals Chondrocytes Humans Lipopolysaccharides Mice Nitric Oxide Nitric Oxide Synthase Type II Osteoarthritis RAW 264.7 Cells Structure-Activity Relationship Anti-Inflammatory Agents Limonene Models, Biological |
topic |
Animals Chondrocytes Humans Lipopolysaccharides Mice Nitric Oxide Nitric Oxide Synthase Type II Osteoarthritis RAW 264.7 Cells Structure-Activity Relationship Anti-Inflammatory Agents Limonene Models, Biological |
description |
Mint species are widely used in traditional and conventional medicine as topical analgesics for osteoarthritic pain and for disorders of the gastrointestinal and respiratory tracts which are all associated with chronic inflammation. To identify the structural determinants of anti-inflammatory activity and potency which are required for chemical optimization towards development of new anti-inflammatory drugs, a selected group of monoterpenes especially abundant in mint species was screened by measuring bacterial lipopolysacharide (LPS)-induced nitric oxide (NO) production in murine macrophages. Nine compounds significantly decreased LPS-induced NO production by more than 30%. IC50 values were calculated showing that the order of potency is: (S)-(+)-carvone > (R)-(-)-carvone > (+)-dihydrocarveol > (S)-8-hydroxycarvotanacetone > (R)-8-hydroxycarvotanacetone > (+)-dihydrocarvone > (-)-carveol > (-)-dihydrocarveol > (S)-(-)-pulegone. Considering the carbon numbering relative to the common precursor, limonene, the presence of an oxygenated group at C6 conjugated to a double bond at C1 and an isopropenyl group and S configuration at C4 are the major chemical features relevant for activity and potency. The most potent compound, (S)-(+)-carvone, significantly decreased the expression of NOS2 and IL-1β in macrophages and in a cell model of osteoarthritis using primary human chondrocytes. (S)-(+)-carvone may be efficient in halting inflammation-related diseases, like osteoarthritis. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-04-29 |
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 |
http://hdl.handle.net/10316/106704 http://hdl.handle.net/10316/106704 https://doi.org/10.1038/s41598-020-64032-1 |
url |
http://hdl.handle.net/10316/106704 https://doi.org/10.1038/s41598-020-64032-1 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
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 |
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1799134118875758592 |