Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade

Detalhes bibliográficos
Autor(a) principal: Jesus, Roberta da Silva
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
dARK ID: ark:/26339/001300000vvwp
Texto Completo: http://repositorio.ufsm.br/handle/1/22082
Resumo: Chenopodium ambrosioides L., popularly known as Erva-de-Santa-Maria, is widely used in folk medicine against many diseases, as anti-inflammatory, healing, among others. In 2009, it was inserted in RENISUS, due to its wide popular use. The aim of this study was to perform the chemical characterization of the irradiated and non-irradiated extracts of C. ambrosioides L., as to elucidate the mechanisms of action involved in the possible anti-inflammatory activity of this species and to determine its safety through in vitro and in vivo assays. The chromatographic profile of the irradiated and non-irradiated extracts was obtained by HPLC-DAD, in order to compare their bioactivity and to verify possible changes in the chemical profile caused by gamma radiation. All samples presented the same qualitative chromatographic profile, but quantitative differences were found between the compounds identified in the extracts. The irradiated plant extract (IPE) showed an increase of canferol derivatives and quercetin derivatives about 20 times more than the other extract. All samples tested were effective in inhibiting LOX at 0.400 - 0.488 mg/mL. Regarding the nitric oxide radical, the non-irradiated plant extract (NIPE) presented the best elimination potential (IC50 value of 0.431 mg / mL). Samples were also evaluated for their toxicity and anti-inflammatory potential in RAW 264.7 macrophages, presenting a safe concentration up to 0.250 mg / mL and NIPE was the most effective in reducing NO in the cell assay (IC50 0.201 ± 0.029 mg / mL). The results obtained in the in vitro analysis appointed the non-irradiated extract for the in vivo study, since it presented a better bioactivity in the performed assays. Mass analysis revealed the presence of 6-hydroxycoumarin, p-coumaric acid, ferulic acid, quercetin-3-O-rutinoside, apigenin, quercitrin, quercitin and canferol. In the acute oral toxicity study, C. ambrosiodies extract was classified as safe (category 5) according to OECD guidelines. Administration of the extract at repeated doses (28 days) only increased AST enzyme activity in females treated with 50 mg / kg. Other toxicological parameters were not altered by extract administration (50-200 mg / kg) in males and females. C. ambrosiodes and B. serrata reduced ear edema induced by croton oil by 47.18 ± 4.59% and 34.23 ± 4.78% (by 1mg / ear), respectively. The same treatments also reduced croton oil-induced inflammatory cell infiltration (observed by myeloperoxidase activity) by 40.71 ± 14.71 for C. ambrosioides (1 mg / ear) and 35.93 ± 9.97% for B. serrata (1 mg / ear). The results obtained in the present study demonstrate the safety profile of C. ambrosioides and its potential as a topical anti-inflammatory agent in the treatment of inflammatory skin disorders, justifying its use in folk medicine.
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spelling Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidadeChenopodium ambrosioides L. from popular use to pre-clinical assays: chemical characterization, safety and determination of its anti-inflammatory activityErva-de-Santa-MariaRadiação ionizanteInflamaçãoToxicidadeIonizing radiationInflammationToxicityCNPQ::CIENCIAS DA SAUDE::FARMACIAChenopodium ambrosioides L., popularly known as Erva-de-Santa-Maria, is widely used in folk medicine against many diseases, as anti-inflammatory, healing, among others. In 2009, it was inserted in RENISUS, due to its wide popular use. The aim of this study was to perform the chemical characterization of the irradiated and non-irradiated extracts of C. ambrosioides L., as to elucidate the mechanisms of action involved in the possible anti-inflammatory activity of this species and to determine its safety through in vitro and in vivo assays. The chromatographic profile of the irradiated and non-irradiated extracts was obtained by HPLC-DAD, in order to compare their bioactivity and to verify possible changes in the chemical profile caused by gamma radiation. All samples presented the same qualitative chromatographic profile, but quantitative differences were found between the compounds identified in the extracts. The irradiated plant extract (IPE) showed an increase of canferol derivatives and quercetin derivatives about 20 times more than the other extract. All samples tested were effective in inhibiting LOX at 0.400 - 0.488 mg/mL. Regarding the nitric oxide radical, the non-irradiated plant extract (NIPE) presented the best elimination potential (IC50 value of 0.431 mg / mL). Samples were also evaluated for their toxicity and anti-inflammatory potential in RAW 264.7 macrophages, presenting a safe concentration up to 0.250 mg / mL and NIPE was the most effective in reducing NO in the cell assay (IC50 0.201 ± 0.029 mg / mL). The results obtained in the in vitro analysis appointed the non-irradiated extract for the in vivo study, since it presented a better bioactivity in the performed assays. Mass analysis revealed the presence of 6-hydroxycoumarin, p-coumaric acid, ferulic acid, quercetin-3-O-rutinoside, apigenin, quercitrin, quercitin and canferol. In the acute oral toxicity study, C. ambrosiodies extract was classified as safe (category 5) according to OECD guidelines. Administration of the extract at repeated doses (28 days) only increased AST enzyme activity in females treated with 50 mg / kg. Other toxicological parameters were not altered by extract administration (50-200 mg / kg) in males and females. C. ambrosiodes and B. serrata reduced ear edema induced by croton oil by 47.18 ± 4.59% and 34.23 ± 4.78% (by 1mg / ear), respectively. The same treatments also reduced croton oil-induced inflammatory cell infiltration (observed by myeloperoxidase activity) by 40.71 ± 14.71 for C. ambrosioides (1 mg / ear) and 35.93 ± 9.97% for B. serrata (1 mg / ear). The results obtained in the present study demonstrate the safety profile of C. ambrosioides and its potential as a topical anti-inflammatory agent in the treatment of inflammatory skin disorders, justifying its use in folk medicine.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESChenopodium ambrosioides L., conhecida popularmente como Erva-de-santa-maria, é amplamente utilizada na medicina popular nas mais diversas enfermidades, anti-inflamatória na cura de feridas, cicatrizante, entre outros. No ano de 2009, foi inserida na RENISUS, devido à sua ampla utilização popular. O objetivo deste estudo foi realizar a caracterização química de extratos irradiados e não irradiados de C. ambrosioides L., bem como elucidar os mecanismos de ação envolvidos na possível atividade anti-inflamatória da espécie e determinar sua segurança através de ensaios in vitro e in vivo. O perfil cromatográfico dos extratos irradiados e não-irradiados foi obtido por CLAE-DAD, com a finalidade de comparar sua bioatividade e verificar possíveis alterações no perfil químico causado pela radiação gama. Todas as amostras apresentaram o mesmo perfil cromatográfico qualitativo, mas foram encontradas diferenças quantitativas entre os compostos identificados nos extratos. O extrato da planta irradiada (EPI) apresentou um aumento de derivados de canferol e derivados de quercetina cerca de 20 vezes do que outros extratos. Todas as amostras testadas foram eficazes na inibição da LOX a 0,400 - 0,488 mg/mL. Em relação ao radical óxido nítrico, o extrato não irradiado (ENI) apresentou o melhor potencial de eliminação (valor IC50 de 0,431 mg / mL). As amostras também foram avaliadas quanto à sua toxicidade e potencial anti-inflamatório nos macrófagos RAW 264.7, apresentando uma concentração segura de até 0,250 mg / mL e o ENI foi o mais efetivo na redução do NO no ensaio celular (IC50 0,201 ± 0,029 mg / mL). Os resultados obtidos nas análises in vitro elegeram o extrato não-irradiado para o estudo in vivo, já que o mesmo apresentou uma melhor bioatividade nos ensaios realizados. A análise de massas revelou a presença de 6-hidroxicumarina, ácido p-cumárico, ácido ferúlico, quercetina-3-O-rutinosídeo, apigenina, quercitrina, quercitina e canferol. No estudo de toxicidade oral aguda, o extrato de C. ambrosiodies foi classificado como seguro (categoria 5) de acordo com as diretrizes da OECD. A administração do extrato em doses repetidas (28 dias) aumentou apenas a atividade da enzima AST, observada em fêmeas tratadas com 50 mg / kg. Outros parâmetros toxicológicos não foram alterados pela administração do extrato (50-200 mg / kg) em machos e fêmeas. C. ambrosiodes e B. serrata reduziram o edema de orelha induzido por óleo de cróton em 47,18 ± 4,59% e 34,23 ± 4,78% (em 1mg / orelha), respectivamente. Os mesmos tratamentos também reduziram a infiltração de células inflamatórias induzida por óleo de cróton (observada pela atividade da mieloperoxidase) em 40,71 ± 14,71 para C. ambrosioides (1 mg / orelha) e 35,93 ± 9,97% para B. serrata (1 mg / orelha). Os resultados obtidos no presente trabalho demonstram o perfil de segurança de C. ambrosioides e seu potencial como agente anti-inflamatório tópico no tratamento de desordens inflamatórias da pele, justificando seu uso na medicina popular.Universidade Federal de Santa MariaBrasilAnálises Clínicas e ToxicológicasUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeBauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968Santos, Roberto Christ Vianna dosSagrillo, Michele RoratoMansur, Michel MachadoMartins, Maria Isabel MorganJesus, Roberta da Silva2021-08-26T20:16:07Z2021-08-26T20:16:07Z2019-08-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/22082ark:/26339/001300000vvwpporAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-08-27T06:03:46Zoai:repositorio.ufsm.br:1/22082Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-08-27T06:03:46Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
Chenopodium ambrosioides L. from popular use to pre-clinical assays: chemical characterization, safety and determination of its anti-inflammatory activity
title Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
spellingShingle Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
Jesus, Roberta da Silva
Erva-de-Santa-Maria
Radiação ionizante
Inflamação
Toxicidade
Ionizing radiation
Inflammation
Toxicity
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
title_full Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
title_fullStr Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
title_full_unstemmed Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
title_sort Chenopodium ambrosioides L. do uso popular aos ensaios pré-clínicos: análise química, potencial anti-inflamatório e estudo da toxicidade
author Jesus, Roberta da Silva
author_facet Jesus, Roberta da Silva
author_role author
dc.contributor.none.fl_str_mv Bauermann, Liliane de Freitas
http://lattes.cnpq.br/5849925846135968
Santos, Roberto Christ Vianna dos
Sagrillo, Michele Rorato
Mansur, Michel Machado
Martins, Maria Isabel Morgan
dc.contributor.author.fl_str_mv Jesus, Roberta da Silva
dc.subject.por.fl_str_mv Erva-de-Santa-Maria
Radiação ionizante
Inflamação
Toxicidade
Ionizing radiation
Inflammation
Toxicity
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Erva-de-Santa-Maria
Radiação ionizante
Inflamação
Toxicidade
Ionizing radiation
Inflammation
Toxicity
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Chenopodium ambrosioides L., popularly known as Erva-de-Santa-Maria, is widely used in folk medicine against many diseases, as anti-inflammatory, healing, among others. In 2009, it was inserted in RENISUS, due to its wide popular use. The aim of this study was to perform the chemical characterization of the irradiated and non-irradiated extracts of C. ambrosioides L., as to elucidate the mechanisms of action involved in the possible anti-inflammatory activity of this species and to determine its safety through in vitro and in vivo assays. The chromatographic profile of the irradiated and non-irradiated extracts was obtained by HPLC-DAD, in order to compare their bioactivity and to verify possible changes in the chemical profile caused by gamma radiation. All samples presented the same qualitative chromatographic profile, but quantitative differences were found between the compounds identified in the extracts. The irradiated plant extract (IPE) showed an increase of canferol derivatives and quercetin derivatives about 20 times more than the other extract. All samples tested were effective in inhibiting LOX at 0.400 - 0.488 mg/mL. Regarding the nitric oxide radical, the non-irradiated plant extract (NIPE) presented the best elimination potential (IC50 value of 0.431 mg / mL). Samples were also evaluated for their toxicity and anti-inflammatory potential in RAW 264.7 macrophages, presenting a safe concentration up to 0.250 mg / mL and NIPE was the most effective in reducing NO in the cell assay (IC50 0.201 ± 0.029 mg / mL). The results obtained in the in vitro analysis appointed the non-irradiated extract for the in vivo study, since it presented a better bioactivity in the performed assays. Mass analysis revealed the presence of 6-hydroxycoumarin, p-coumaric acid, ferulic acid, quercetin-3-O-rutinoside, apigenin, quercitrin, quercitin and canferol. In the acute oral toxicity study, C. ambrosiodies extract was classified as safe (category 5) according to OECD guidelines. Administration of the extract at repeated doses (28 days) only increased AST enzyme activity in females treated with 50 mg / kg. Other toxicological parameters were not altered by extract administration (50-200 mg / kg) in males and females. C. ambrosiodes and B. serrata reduced ear edema induced by croton oil by 47.18 ± 4.59% and 34.23 ± 4.78% (by 1mg / ear), respectively. The same treatments also reduced croton oil-induced inflammatory cell infiltration (observed by myeloperoxidase activity) by 40.71 ± 14.71 for C. ambrosioides (1 mg / ear) and 35.93 ± 9.97% for B. serrata (1 mg / ear). The results obtained in the present study demonstrate the safety profile of C. ambrosioides and its potential as a topical anti-inflammatory agent in the treatment of inflammatory skin disorders, justifying its use in folk medicine.
publishDate 2019
dc.date.none.fl_str_mv 2019-08-19
2021-08-26T20:16:07Z
2021-08-26T20:16:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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url http://repositorio.ufsm.br/handle/1/22082
identifier_str_mv ark:/26339/001300000vvwp
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Análises Clínicas e Toxicológicas
UFSM
Programa de Pós-Graduação em Ciências Farmacêuticas
Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Análises Clínicas e Toxicológicas
UFSM
Programa de Pós-Graduação em Ciências Farmacêuticas
Centro de Ciências da Saúde
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
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instname_str Universidade Federal de Santa Maria (UFSM)
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institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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