Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica

Detalhes bibliográficos
Autor(a) principal: Oliveira, Alan Santos
Data de Publicação: 2022
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: http://ri.ufs.br/jspui/handle/riufs/16772
Resumo: Introduction: Rambutan, the fruit of Nephelium lappaceum L. (Sapindaceae) is popularly used to treat fever, stomach pain and diarrhea. The peels of rambutan contain a variety of phytochemicals, such as phenolic compounds, flavonoids and carotenoids, which add potential for several biological activities. Its use is suggested in cosmeceutical, nutraceutical and pharmaceutical preparations. Objective: The present study evaluated the antinociceptive and gastroprotective activities of the ethanolic extract of the fruit peels of N. lappaceum L. (EENL) in non-clinical models, as well as it evaluated whether this extract induces acute toxicity in zebrafish. Material and methods: EENL was characterized by chromatography coupled to mass spectrometry (RP-UHPLC-DAD). The experimental protocols were approved by the Animal Research Ethics Committee of Instituto Butantan – São Paulo (nº 6438210220) and UFS (nº 1122270819). An acute toxicity test was performed on zebrafish. Male Swiss mice were treated with EENL (50, 100 or 200 mg/kg, po, 1 hour before) and submitted to nociception assessment (abdominal writhing, paw formalin and capsaicin, carrageenan-induced mechanical hyperalgesia and hot plate test) and locomotor activity (open field). The ulcer model induced by acidified ethanol (60% ethanol/0.3 mol/L HCl) was used to evaluate the gastroprotective effect of EENL. In this model, the concentration of sulfhydryl compounds and lipid peroxidation in the gastric mucosa were also evaluated. The participation of non-protein sulfhydryl compounds (NP-SH), nitric oxide (NO), prostaglandins (PG), ATP-sensitive K+ channels (KATP) and hydrogen sulfide (H2S) in the gastroprotective effect of EENL was investigated in this model of ulcer using pharmacological tools. The effect of EENL on gastric volume, acidity and pH was evaluated in the pylorus ligation model, as well as mucus on gastric contents. Results: Procyanidin B, epicatechin, ellagic acid and their derivatives (such as punicalin and pedunculagin) were identified in the EENL. No toxicity was observed after incubating EENL with zebrafish embryos. Oral pretreatment of mice with EENL (200 mg/kg) did not alter locomotor activity, but pretreatment with doses of 50, 100 and 200 mg/kg reduced (p<0.05 or p<0.001) the abdominal writhing induced by acetic acid. Pretreatment with EENL (100 and 200 mg/kg, p.o.) reduced (p<0.001) the licking/biting time in both first and second phases of the formalin test and in the capsaicin test, as well as decreased (p<0.001) carrageenan-induced mechanical paw hyperalgesia. In the hot plate test, oral pretreatment with EENL (50,100 and 200 mg/kg) increased (p<0.001) the latency time. This antinociceptive effect was reversed by naloxone (opioid antagonist), L-arginine (a precursor of nitric oxide) and glibenclamide (a KATP blocker). Pretreatment with EENL (50, 100 and 200 mg/kg) reduced the area of gastric injury induced by acidified ethanol (p<0.01) and lipid peroxidation (p<0.001), and the doses of 100 and 200 mg/kg increased sulfhydryl content in the stomach (p<0.01 or 0.05, respectively) compared to the vehicle group. Pretreatment with N-ethylmaleimide (a non-protein sulfhydryl group blocker, 10 mg/kg, ip), indomethacin (inhibitor of prostaglandin synthesis, 10 mg/kg) or L-NAME (inhibitor of nitric oxide synthase, 70 mg/kg) inhibited the gastroprotective response caused by EENL (100 mg/kg; p<0.05 or 0.001), but there were no changes due to pretreatments with glibenclamide (a KATP channel blocker, 10 mg/kg, ip) or DL-propargylglycine (an inhibitor of hydrogen sulfide synthesis, 10 mg/kg). In addition, treatment with EENL (100 mg/kg) increased mucus production (p<0.001) and pH (p<0.01) and reduced the volume (p<0.001) and acidity (p<0.001) of the gastric secretion after pylorus ligation. Conclusion: The results demonstrate that EENL did not cause changes in zebrafish, contains anthocyanins, catechins and phenolic compounds, induces antinociceptive effect with the participation of opioid receptors, NO and KATP channels and promotes gastroprotective effect with the participation of sulfhydryl groups, prostaglandins, NO and increased mucus production and modulation of parameters of gastric secretion.
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spelling Oliveira, Alan SantosCamargo, Enilton Aparecido2022-11-18T18:59:11Z2022-11-18T18:59:11Z2022OLIVEIRA, Alan Santos. Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica. 2022. 160 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, SE, 2022.http://ri.ufs.br/jspui/handle/riufs/16772Introduction: Rambutan, the fruit of Nephelium lappaceum L. (Sapindaceae) is popularly used to treat fever, stomach pain and diarrhea. The peels of rambutan contain a variety of phytochemicals, such as phenolic compounds, flavonoids and carotenoids, which add potential for several biological activities. Its use is suggested in cosmeceutical, nutraceutical and pharmaceutical preparations. Objective: The present study evaluated the antinociceptive and gastroprotective activities of the ethanolic extract of the fruit peels of N. lappaceum L. (EENL) in non-clinical models, as well as it evaluated whether this extract induces acute toxicity in zebrafish. Material and methods: EENL was characterized by chromatography coupled to mass spectrometry (RP-UHPLC-DAD). The experimental protocols were approved by the Animal Research Ethics Committee of Instituto Butantan – São Paulo (nº 6438210220) and UFS (nº 1122270819). An acute toxicity test was performed on zebrafish. Male Swiss mice were treated with EENL (50, 100 or 200 mg/kg, po, 1 hour before) and submitted to nociception assessment (abdominal writhing, paw formalin and capsaicin, carrageenan-induced mechanical hyperalgesia and hot plate test) and locomotor activity (open field). The ulcer model induced by acidified ethanol (60% ethanol/0.3 mol/L HCl) was used to evaluate the gastroprotective effect of EENL. In this model, the concentration of sulfhydryl compounds and lipid peroxidation in the gastric mucosa were also evaluated. The participation of non-protein sulfhydryl compounds (NP-SH), nitric oxide (NO), prostaglandins (PG), ATP-sensitive K+ channels (KATP) and hydrogen sulfide (H2S) in the gastroprotective effect of EENL was investigated in this model of ulcer using pharmacological tools. The effect of EENL on gastric volume, acidity and pH was evaluated in the pylorus ligation model, as well as mucus on gastric contents. Results: Procyanidin B, epicatechin, ellagic acid and their derivatives (such as punicalin and pedunculagin) were identified in the EENL. No toxicity was observed after incubating EENL with zebrafish embryos. Oral pretreatment of mice with EENL (200 mg/kg) did not alter locomotor activity, but pretreatment with doses of 50, 100 and 200 mg/kg reduced (p<0.05 or p<0.001) the abdominal writhing induced by acetic acid. Pretreatment with EENL (100 and 200 mg/kg, p.o.) reduced (p<0.001) the licking/biting time in both first and second phases of the formalin test and in the capsaicin test, as well as decreased (p<0.001) carrageenan-induced mechanical paw hyperalgesia. In the hot plate test, oral pretreatment with EENL (50,100 and 200 mg/kg) increased (p<0.001) the latency time. This antinociceptive effect was reversed by naloxone (opioid antagonist), L-arginine (a precursor of nitric oxide) and glibenclamide (a KATP blocker). Pretreatment with EENL (50, 100 and 200 mg/kg) reduced the area of gastric injury induced by acidified ethanol (p<0.01) and lipid peroxidation (p<0.001), and the doses of 100 and 200 mg/kg increased sulfhydryl content in the stomach (p<0.01 or 0.05, respectively) compared to the vehicle group. Pretreatment with N-ethylmaleimide (a non-protein sulfhydryl group blocker, 10 mg/kg, ip), indomethacin (inhibitor of prostaglandin synthesis, 10 mg/kg) or L-NAME (inhibitor of nitric oxide synthase, 70 mg/kg) inhibited the gastroprotective response caused by EENL (100 mg/kg; p<0.05 or 0.001), but there were no changes due to pretreatments with glibenclamide (a KATP channel blocker, 10 mg/kg, ip) or DL-propargylglycine (an inhibitor of hydrogen sulfide synthesis, 10 mg/kg). In addition, treatment with EENL (100 mg/kg) increased mucus production (p<0.001) and pH (p<0.01) and reduced the volume (p<0.001) and acidity (p<0.001) of the gastric secretion after pylorus ligation. Conclusion: The results demonstrate that EENL did not cause changes in zebrafish, contains anthocyanins, catechins and phenolic compounds, induces antinociceptive effect with the participation of opioid receptors, NO and KATP channels and promotes gastroprotective effect with the participation of sulfhydryl groups, prostaglandins, NO and increased mucus production and modulation of parameters of gastric secretion.Introdução: O rambutan, fruto de Nephelium lappaceum L. (Sapindaceae) é utilizado popularmente para tratar febre, dor no estômago e diarreia. Suas cascas contêm uma variedade de fitoquímicos, como compostos fenólicos, flavonoides e carotenoides, o que lhe atribui diversas atividades biológicas, sendo sugerido seu uso em preparações cosmecêuticas, nutracêuticas e farmacêuticas. Objetivo: O presente estudo avaliou as atividades antinociceptiva e gastroprotetora do extrato etanólico das cascas do fruto de N. lappaceum L. (EENL) em modelos não clínicos, bem como avaliou se este extrato induz toxicidade aguda em zebrafish. Material e métodos: O EENL foi caracterizado por cromatografia acoplada a espectrometria de massa (RP-UHPLC-DAD). Os protocolos experimentais foram aprovados pelo Comitê de Ética Uso de Animais do Instituto Butantan – São Paulo (nº 6438210220) e da UFS (nº 1122270819). Foi realizado o ensaio de toxicidade aguda em zebrafish. Camundongos Swiss machos foram tratados com EENL (50, 100 ou 200 mg/kg, v.o., 1 hora antes) e submetidos à avaliação de nocicepção (contorções abdominais, formalina e capsaicina na pata, hiperalgesia mecânica induzida por carragenina e teste de placa quente) e atividade locomotora (campo aberto). O modelo de úlcera induzida por etanol acidificado (etanol a 60%/HCl a 0,3 mol/L) foi utilizado para avaliar o efeito gastroprotetor do EENL. Neste modelo, também foi avaliada a concentração dos compostos sulfidrílicos e a peroxidação lipídica na mucosa gástrica. A participação dos compostos sulfidrílicos não proteicos (NP-SH), óxido nítrico (NO), prostaglandinas (PG), canais para K+ sensíveis ao ATP (KATP) e sulfeto de hidrogênio (H2S) no efeito gastroprotetor do EENL foi investigada neste modelo de úlcera pelo uso de ferramentas farmacológicas. O efeito do EENL sobre o volume, a acidez e o pH gástricos foi avaliado no modelo de ligadura do piloro, bem como o muco no conteúdo gástrico. Resultados: Procianidina B, epicatequina, ácido elágico e seus derivados (como punicalina e pedunculagina) foram identificados no EENL. Não foi observado toxicidade alguma após incubar o EENL com embriões de zebrafish. O pré-tratamento oral de camundongos com EENL (200 mg/kg) não alterou a atividade locomotora, mas as doses de 50, 100 e 200 mg/kg reduziram (p<0,05 ou p<0,001) as contorções abdominais induzidas por ácido acético. O pré-tratamento com EENL (100 e 200 mg/kg, v.o.) reduziu (p <0,001) o tempo de lambida/mordida na primeira e na segunda fase do teste de formalina e no teste de capsaicina, bem como diminuiu (p<0,001) a hiperalgesia mecânica da pata induzida por carragenina. No teste da placa quente, o pré-tratamento oral com EENL (50,100 e 200 mg/kg) aumentou (p<0,001) o tempo de latência. Este efeito antinociceptivo foi revertido pela naloxona (antagonista opioide), L-arginina (um precursor do óxido nítrico) e glibenclamida (um bloqueador de KATP). O pré-tratamento com EENL (50, 100 e 200 mg/kg) reduziu a área de lesão gástrica induzida pelo etanol acidificado (p<0,01) e a lipoperoxidação (p <0,001), e as doses de 100 e 200 mg/kg aumentaram o conteúdo de sulfidrila (p<0,01 ou 0,05, respectivamente) no estômago em comparação com o grupo veículo. O pré-tratamento com N-etilmaleimida (um bloqueador de grupos sulfidrila não proteicos, 10 mg/kg, ip), indometacina (inibidora da síntese de prostaglandinas, 10 mg/kg) ou L-NAME (inibidor das sintases de óxido nítrico, 70 mg/kg) inibiu a resposta gastroprotetora causada por EENL (100 mg/kg; p<0,05 ou 0,001), mas não houve alteração devido aos pré-tratamentos com glibenclamida (um bloqueador de KATP, 10 mg/kg, ip) ou DL-propargilglicina (um inibidor da síntese de sulfeto de hidrogênio, 10 mg/kg). Além disso, o tratamento com EENL (100 mg/kg) aumentou a produção de muco (p<0,001) e o pH (p<0,01) e reduziu o volume (p<0,001) e a acidez (p<0,001) da secreção gástrica após a ligadura do piloro. Conclusão: Os resultados demonstram que o EENL não causou alterações em zebrafish, contém antocianinas, catequinas e outros compostos fenólicos, induz efeito antinociceptivo com a participação de receptores opioides, NO e KATP, promove efeito gastroprotetor com a participação de grupos sulfidrila, prostaglandinas e NO e do aumento da produção de muco e modulação dos parâmetros de secreção gástrica.AracajuporRabutanAtividade motoraToxidadeMucosa gástricaÚlcera gástricaLocomotor activityToxicityGastric mucosaGastric ulcerCIENCIAS DA SAUDEEfeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástricaPharmacological effects of the ethanolic extract of the fruit peels of Nephelium lappaceum L. on nociception and gastric ulcerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Ciências da SaúdeUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/16772/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALAlan_Santos_Oliveira.pdfAlan_Santos_Oliveira.pdfapplication/pdf6107960https://ri.ufs.br/jspui/bitstream/riufs/16772/2/Alan_Santos_Oliveira.pdfc6faee1c961fe5032603fe970d328557MD52TEXTAlan_Santos_Oliveira.pdf.txtAlan_Santos_Oliveira.pdf.txtExtracted texttext/plain275019https://ri.ufs.br/jspui/bitstream/riufs/16772/3/Alan_Santos_Oliveira.pdf.txt228eaefc31f0b2b0891a0e1be59f9e9eMD53THUMBNAILAlan_Santos_Oliveira.pdf.jpgAlan_Santos_Oliveira.pdf.jpgGenerated Thumbnailimage/jpeg1194https://ri.ufs.br/jspui/bitstream/riufs/16772/4/Alan_Santos_Oliveira.pdf.jpg7e5a5bc38bc12e2669f60920136f0f1bMD54riufs/167722022-11-18 15:59:11.929oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2022-11-18T18:59:11Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
dc.title.alternative.por.fl_str_mv Pharmacological effects of the ethanolic extract of the fruit peels of Nephelium lappaceum L. on nociception and gastric ulcer
title Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
spellingShingle Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
Oliveira, Alan Santos
Rabutan
Atividade motora
Toxidade
Mucosa gástrica
Úlcera gástrica
Locomotor activity
Toxicity
Gastric mucosa
Gastric ulcer
CIENCIAS DA SAUDE
title_short Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
title_full Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
title_fullStr Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
title_full_unstemmed Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
title_sort Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica
author Oliveira, Alan Santos
author_facet Oliveira, Alan Santos
author_role author
dc.contributor.author.fl_str_mv Oliveira, Alan Santos
dc.contributor.advisor1.fl_str_mv Camargo, Enilton Aparecido
contributor_str_mv Camargo, Enilton Aparecido
dc.subject.por.fl_str_mv Rabutan
Atividade motora
Toxidade
Mucosa gástrica
Úlcera gástrica
topic Rabutan
Atividade motora
Toxidade
Mucosa gástrica
Úlcera gástrica
Locomotor activity
Toxicity
Gastric mucosa
Gastric ulcer
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv Locomotor activity
Toxicity
Gastric mucosa
Gastric ulcer
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Introduction: Rambutan, the fruit of Nephelium lappaceum L. (Sapindaceae) is popularly used to treat fever, stomach pain and diarrhea. The peels of rambutan contain a variety of phytochemicals, such as phenolic compounds, flavonoids and carotenoids, which add potential for several biological activities. Its use is suggested in cosmeceutical, nutraceutical and pharmaceutical preparations. Objective: The present study evaluated the antinociceptive and gastroprotective activities of the ethanolic extract of the fruit peels of N. lappaceum L. (EENL) in non-clinical models, as well as it evaluated whether this extract induces acute toxicity in zebrafish. Material and methods: EENL was characterized by chromatography coupled to mass spectrometry (RP-UHPLC-DAD). The experimental protocols were approved by the Animal Research Ethics Committee of Instituto Butantan – São Paulo (nº 6438210220) and UFS (nº 1122270819). An acute toxicity test was performed on zebrafish. Male Swiss mice were treated with EENL (50, 100 or 200 mg/kg, po, 1 hour before) and submitted to nociception assessment (abdominal writhing, paw formalin and capsaicin, carrageenan-induced mechanical hyperalgesia and hot plate test) and locomotor activity (open field). The ulcer model induced by acidified ethanol (60% ethanol/0.3 mol/L HCl) was used to evaluate the gastroprotective effect of EENL. In this model, the concentration of sulfhydryl compounds and lipid peroxidation in the gastric mucosa were also evaluated. The participation of non-protein sulfhydryl compounds (NP-SH), nitric oxide (NO), prostaglandins (PG), ATP-sensitive K+ channels (KATP) and hydrogen sulfide (H2S) in the gastroprotective effect of EENL was investigated in this model of ulcer using pharmacological tools. The effect of EENL on gastric volume, acidity and pH was evaluated in the pylorus ligation model, as well as mucus on gastric contents. Results: Procyanidin B, epicatechin, ellagic acid and their derivatives (such as punicalin and pedunculagin) were identified in the EENL. No toxicity was observed after incubating EENL with zebrafish embryos. Oral pretreatment of mice with EENL (200 mg/kg) did not alter locomotor activity, but pretreatment with doses of 50, 100 and 200 mg/kg reduced (p<0.05 or p<0.001) the abdominal writhing induced by acetic acid. Pretreatment with EENL (100 and 200 mg/kg, p.o.) reduced (p<0.001) the licking/biting time in both first and second phases of the formalin test and in the capsaicin test, as well as decreased (p<0.001) carrageenan-induced mechanical paw hyperalgesia. In the hot plate test, oral pretreatment with EENL (50,100 and 200 mg/kg) increased (p<0.001) the latency time. This antinociceptive effect was reversed by naloxone (opioid antagonist), L-arginine (a precursor of nitric oxide) and glibenclamide (a KATP blocker). Pretreatment with EENL (50, 100 and 200 mg/kg) reduced the area of gastric injury induced by acidified ethanol (p<0.01) and lipid peroxidation (p<0.001), and the doses of 100 and 200 mg/kg increased sulfhydryl content in the stomach (p<0.01 or 0.05, respectively) compared to the vehicle group. Pretreatment with N-ethylmaleimide (a non-protein sulfhydryl group blocker, 10 mg/kg, ip), indomethacin (inhibitor of prostaglandin synthesis, 10 mg/kg) or L-NAME (inhibitor of nitric oxide synthase, 70 mg/kg) inhibited the gastroprotective response caused by EENL (100 mg/kg; p<0.05 or 0.001), but there were no changes due to pretreatments with glibenclamide (a KATP channel blocker, 10 mg/kg, ip) or DL-propargylglycine (an inhibitor of hydrogen sulfide synthesis, 10 mg/kg). In addition, treatment with EENL (100 mg/kg) increased mucus production (p<0.001) and pH (p<0.01) and reduced the volume (p<0.001) and acidity (p<0.001) of the gastric secretion after pylorus ligation. Conclusion: The results demonstrate that EENL did not cause changes in zebrafish, contains anthocyanins, catechins and phenolic compounds, induces antinociceptive effect with the participation of opioid receptors, NO and KATP channels and promotes gastroprotective effect with the participation of sulfhydryl groups, prostaglandins, NO and increased mucus production and modulation of parameters of gastric secretion.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-11-18T18:59:11Z
dc.date.available.fl_str_mv 2022-11-18T18:59:11Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv OLIVEIRA, Alan Santos. Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica. 2022. 160 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, SE, 2022.
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/16772
identifier_str_mv OLIVEIRA, Alan Santos. Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica. 2022. 160 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, SE, 2022.
url http://ri.ufs.br/jspui/handle/riufs/16772
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