Effects of Polymethoxylated Flavone Metabolites on ApoB100 Secretion and MTP Activity in Huh7.5 Cells

Detalhes bibliográficos
Autor(a) principal: Gonçalves, Danielle R. [UNESP]
Data de Publicação: 2022
Outros Autores: Cesar, Thais B. [UNESP], Manthey, John A., Costa, Paulo I. [UNESP]
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.
id UNSP_b763910cc74d7ab5fbe47bde7535c236
oai_identifier_str oai:repositorio.unesp.br:11449/240383
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling 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
_version_ 1808128580418273280