Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.2174/1573407218666211230140952 http://hdl.handle.net/11449/240383 |
Resumo: | Background: Citrus polymethoxylated flavones (PMFs) reduce the synthesis of liver lipoproteins in animal and in vitro cell assays, but few studies have evaluated the direct effects of their metabolites on this highly regulated process. Objective: The aim of the study was to investigate the effects of representative metabolites of PMF on the secretion of liver lipoproteins using the mammalian cell Huh7.5. Methods: In this study, the influences of three PMFs and five previously isolated PMF metabolites on hepatic apoB-100 secretion and microsomal transfer protein (MTP) activity were evaluated. Tangeretin (TAN), nobiletin (NOB) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), their glucuronides (TAN-Gluc, NOB-Gluc and HMF-Gluc) and oxidatively demethylated metabolites (TAN-OH, NOB-OH, HMF-OH), were incubated with Huh7.5 cells to measure their inhibitory effects on lipid synthesis. Results: The results showed that TAN, HMF and TAN-OH reduced the secretion of apoB-100 in a dose-dependent manner, while NOB and the other tested metabolites showed no inhibition. MTP activity in the Huh7.5 cells was significantly reduced in the presence of low concentrations of TAN and high concentrations of NOB-OH. This study also showed that PMFs and PMF metabolites produced a wide range of effects on apoB-100 secretion and MTP activity. Conclusion: The results suggest that while PMFs and their metabolites control dyslipidemia in vivo, the inhibition of MTP activity cannot be the only pathway influenced by these compounds. |
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Repositório Institucional da UNESP |
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Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cellsdemethylated PMF metabolitesglucuronide PMF metabolitesHepatic lipidsheptamethoxyflavonenobiletintangeretinBackground: Citrus polymethoxylated flavones (PMFs) reduce the synthesis of liver lipoproteins in animal and in vitro cell assays, but few studies have evaluated the direct effects of their metabolites on this highly regulated process. Objective: The aim of the study was to investigate the effects of representative metabolites of PMF on the secretion of liver lipoproteins using the mammalian cell Huh7.5. Methods: In this study, the influences of three PMFs and five previously isolated PMF metabolites on hepatic apoB-100 secretion and microsomal transfer protein (MTP) activity were evaluated. Tangeretin (TAN), nobiletin (NOB) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), their glucuronides (TAN-Gluc, NOB-Gluc and HMF-Gluc) and oxidatively demethylated metabolites (TAN-OH, NOB-OH, HMF-OH), were incubated with Huh7.5 cells to measure their inhibitory effects on lipid synthesis. Results: The results showed that TAN, HMF and TAN-OH reduced the secretion of apoB-100 in a dose-dependent manner, while NOB and the other tested metabolites showed no inhibition. MTP activity in the Huh7.5 cells was significantly reduced in the presence of low concentrations of TAN and high concentrations of NOB-OH. This study also showed that PMFs and PMF metabolites produced a wide range of effects on apoB-100 secretion and MTP activity. Conclusion: The results suggest that while PMFs and their metabolites control dyslipidemia in vivo, the inhibition of MTP activity cannot be the only pathway influenced by these compounds.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)School of Pharmaceutical Sciences Sao Paulo State University-UNESP, Rodovia Araraquara-Jau km1, SPU.S. Horticultural Research Laboratory Agricultural Research Service U.S. Department of Agriculture, 2001 South Rock RoadSchool of Pharmaceutical Sciences Sao Paulo State University-UNESP, Rodovia Araraquara-Jau km1, SPUniversidade Estadual Paulista (UNESP)U.S. Department of AgricultureGonçalves, Danielle R. [UNESP]Cesar, Thais B. [UNESP]Manthey, John A.Costa, Paulo I. [UNESP]2023-03-01T20:14:47Z2023-03-01T20:14:47Z2022-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.2174/1573407218666211230140952Current Bioactive Compounds, v. 18, n. 6, 2022.1875-66461573-4072http://hdl.handle.net/11449/24038310.2174/15734072186662112301409522-s2.0-85133371676Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCurrent Bioactive Compoundsinfo:eu-repo/semantics/openAccess2023-03-01T20:14:47Zoai:repositorio.unesp.br:11449/240383Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:53:51.455147Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells |
title |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells |
spellingShingle |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells Gonçalves, Danielle R. [UNESP] demethylated PMF metabolites glucuronide PMF metabolites Hepatic lipids heptamethoxyflavone nobiletin tangeretin |
title_short |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells |
title_full |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells |
title_fullStr |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells |
title_full_unstemmed |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells |
title_sort |
Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells |
author |
Gonçalves, Danielle R. [UNESP] |
author_facet |
Gonçalves, Danielle R. [UNESP] Cesar, Thais B. [UNESP] Manthey, John A. Costa, Paulo I. [UNESP] |
author_role |
author |
author2 |
Cesar, Thais B. [UNESP] Manthey, John A. Costa, Paulo I. [UNESP] |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) U.S. Department of Agriculture |
dc.contributor.author.fl_str_mv |
Gonçalves, Danielle R. [UNESP] Cesar, Thais B. [UNESP] Manthey, John A. Costa, Paulo I. [UNESP] |
dc.subject.por.fl_str_mv |
demethylated PMF metabolites glucuronide PMF metabolites Hepatic lipids heptamethoxyflavone nobiletin tangeretin |
topic |
demethylated PMF metabolites glucuronide PMF metabolites Hepatic lipids heptamethoxyflavone nobiletin tangeretin |
description |
Background: Citrus polymethoxylated flavones (PMFs) reduce the synthesis of liver lipoproteins in animal and in vitro cell assays, but few studies have evaluated the direct effects of their metabolites on this highly regulated process. Objective: The aim of the study was to investigate the effects of representative metabolites of PMF on the secretion of liver lipoproteins using the mammalian cell Huh7.5. Methods: In this study, the influences of three PMFs and five previously isolated PMF metabolites on hepatic apoB-100 secretion and microsomal transfer protein (MTP) activity were evaluated. Tangeretin (TAN), nobiletin (NOB) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), their glucuronides (TAN-Gluc, NOB-Gluc and HMF-Gluc) and oxidatively demethylated metabolites (TAN-OH, NOB-OH, HMF-OH), were incubated with Huh7.5 cells to measure their inhibitory effects on lipid synthesis. Results: The results showed that TAN, HMF and TAN-OH reduced the secretion of apoB-100 in a dose-dependent manner, while NOB and the other tested metabolites showed no inhibition. MTP activity in the Huh7.5 cells was significantly reduced in the presence of low concentrations of TAN and high concentrations of NOB-OH. This study also showed that PMFs and PMF metabolites produced a wide range of effects on apoB-100 secretion and MTP activity. Conclusion: The results suggest that while PMFs and their metabolites control dyslipidemia in vivo, the inhibition of MTP activity cannot be the only pathway influenced by these compounds. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-07-01 2023-03-01T20:14:47Z 2023-03-01T20:14:47Z |
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/10.2174/1573407218666211230140952 Current Bioactive Compounds, v. 18, n. 6, 2022. 1875-6646 1573-4072 http://hdl.handle.net/11449/240383 10.2174/1573407218666211230140952 2-s2.0-85133371676 |
url |
http://dx.doi.org/10.2174/1573407218666211230140952 http://hdl.handle.net/11449/240383 |
identifier_str_mv |
Current Bioactive Compounds, v. 18, n. 6, 2022. 1875-6646 1573-4072 10.2174/1573407218666211230140952 2-s2.0-85133371676 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Current Bioactive Compounds |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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 |
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1808128580418273280 |