Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity

Detalhes bibliográficos
Autor(a) principal: Sousa, Cátia
Data de Publicação: 2020
Outros Autores: Leitão, Alcino Jorge, Neves, Bruno Miguel, Judas, Fernando, Cavaleiro, Carlos, Mendes, Alexandrina F.
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.
id RCAP_d7533ca153d389f68767e0da9bf97114
oai_identifier_str oai:estudogeral.uc.pt:10316/106704
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 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
_version_ 1799134118875758592