Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/ijms18091972 http://hdl.handle.net/11449/175185 |
Resumo: | Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1β production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 µg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins. |
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Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edemaEdemaFlavonoidMyonecrosisPeperomia obtusifoliaPiperaceaeSnake venom phospholipase A2Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1β production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 µg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Curso de Química Universidade Presbiteriana Mackenzie, Rua da ConsolaçãoFaculdade de Odontologia Universidade Camilo Castelo Branco (UNICASTELO)Universidade Estadual Paulista (UNESP) Campus do Litoral Paulista, Praça Infante Dom Henrique s/n Bairro: Parque BitaruInstituto de Biologia Universidade do Estado do Rio de Janeiro (UERJ)Departamento de Botância Instituto de Biociências University of São PauloUniversidade Estadual Paulista (UNESP) Campus do Litoral Paulista, Praça Infante Dom Henrique s/n Bairro: Parque BitaruUniversidade Presbiteriana MackenzieUniversidade Camilo Castelo Branco (UNICASTELO)Universidade Estadual Paulista (Unesp)Universidade do Estado do Rio de Janeiro (UERJ)Universidade de São Paulo (USP)Tamayose, Cinthia I.Romoff, PauleteToyama, Daniela O.Gaeta, Henrique H. [UNESP]Costa, Caroline R. C. [UNESP]Belchor, Mariana N. [UNESP]Ortolan, Bruna D. [UNESP]Velozo, Leosvaldo S. M.Kaplan, Maria A. C.Ferreira, Marcelo J. P.Toyama, Marcos H. [UNESP]2018-12-11T17:14:44Z2018-12-11T17:14:44Z2017-09-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.3390/ijms18091972International Journal of Molecular Sciences, v. 18, n. 9, 2017.1422-00671661-6596http://hdl.handle.net/11449/17518510.3390/ijms180919722-s2.0-850296145222-s2.0-85029614522.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Sciences1,260info:eu-repo/semantics/openAccess2023-12-21T06:19:14Zoai:repositorio.unesp.br:11449/175185Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-21T06:19:14Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema |
title |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema |
spellingShingle |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema Tamayose, Cinthia I. Edema Flavonoid Myonecrosis Peperomia obtusifolia Piperaceae Snake venom phospholipase A2 |
title_short |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema |
title_full |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema |
title_fullStr |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema |
title_full_unstemmed |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema |
title_sort |
Non-clinical studies for evaluation of 8-C-rhamnosyl apigenin purified from peperomia obtusifolia against acute edema |
author |
Tamayose, Cinthia I. |
author_facet |
Tamayose, Cinthia I. Romoff, Paulete Toyama, Daniela O. Gaeta, Henrique H. [UNESP] Costa, Caroline R. C. [UNESP] Belchor, Mariana N. [UNESP] Ortolan, Bruna D. [UNESP] Velozo, Leosvaldo S. M. Kaplan, Maria A. C. Ferreira, Marcelo J. P. Toyama, Marcos H. [UNESP] |
author_role |
author |
author2 |
Romoff, Paulete Toyama, Daniela O. Gaeta, Henrique H. [UNESP] Costa, Caroline R. C. [UNESP] Belchor, Mariana N. [UNESP] Ortolan, Bruna D. [UNESP] Velozo, Leosvaldo S. M. Kaplan, Maria A. C. Ferreira, Marcelo J. P. Toyama, Marcos H. [UNESP] |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Presbiteriana Mackenzie Universidade Camilo Castelo Branco (UNICASTELO) Universidade Estadual Paulista (Unesp) Universidade do Estado do Rio de Janeiro (UERJ) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Tamayose, Cinthia I. Romoff, Paulete Toyama, Daniela O. Gaeta, Henrique H. [UNESP] Costa, Caroline R. C. [UNESP] Belchor, Mariana N. [UNESP] Ortolan, Bruna D. [UNESP] Velozo, Leosvaldo S. M. Kaplan, Maria A. C. Ferreira, Marcelo J. P. Toyama, Marcos H. [UNESP] |
dc.subject.por.fl_str_mv |
Edema Flavonoid Myonecrosis Peperomia obtusifolia Piperaceae Snake venom phospholipase A2 |
topic |
Edema Flavonoid Myonecrosis Peperomia obtusifolia Piperaceae Snake venom phospholipase A2 |
description |
Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1β production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 µg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-09-14 2018-12-11T17:14:44Z 2018-12-11T17:14:44Z |
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://dx.doi.org/10.3390/ijms18091972 International Journal of Molecular Sciences, v. 18, n. 9, 2017. 1422-0067 1661-6596 http://hdl.handle.net/11449/175185 10.3390/ijms18091972 2-s2.0-85029614522 2-s2.0-85029614522.pdf |
url |
http://dx.doi.org/10.3390/ijms18091972 http://hdl.handle.net/11449/175185 |
identifier_str_mv |
International Journal of Molecular Sciences, v. 18, n. 9, 2017. 1422-0067 1661-6596 10.3390/ijms18091972 2-s2.0-85029614522 2-s2.0-85029614522.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Molecular Sciences 1,260 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965354541187072 |