Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo

ABSTARCT: The accumulation of oxidized ApoB-100-containing lipoproteins in the vascular intima and its subsequent recognition by macrophages results in foam cell formation and inflammation, key events during atherosclerosis development. Agents targeting this process are considered potentially athero...

Full description

Autores:
Lara Guzmán, Oscar Javier
Tabares Guevara, Jorge Humberto
Sierra Restrepo, Jelver Alexander
Londoño Londoño, Julián Alberto
Álvarez Quintero, Rafael Mariano
León Varela, Yudy Milena
Osorio Durango, Edison Javier
Ramírez Pineda, José Robinson
Tipo de recurso:
Article of investigation
Fecha de publicación:
2017
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/11641
Acceso en línea:
http://hdl.handle.net/10495/11641
Palabra clave:
Garcinia madruno
Atherosclerosis
Biflavonoid
Foam cell
Macrophage
Morelloflavone
Oxidized LDL
Volkensiflavone
Rights
openAccess
License
Atribución 2.5
id UDEA2_82c20c30e01f1dbd2ca651b16da1af58
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/11641
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
title Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
spellingShingle Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
Garcinia madruno
Atherosclerosis
Biflavonoid
Foam cell
Macrophage
Morelloflavone
Oxidized LDL
Volkensiflavone
title_short Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
title_full Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
title_fullStr Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
title_full_unstemmed Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
title_sort Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo
dc.creator.fl_str_mv Lara Guzmán, Oscar Javier
Tabares Guevara, Jorge Humberto
Sierra Restrepo, Jelver Alexander
Londoño Londoño, Julián Alberto
Álvarez Quintero, Rafael Mariano
León Varela, Yudy Milena
Osorio Durango, Edison Javier
Ramírez Pineda, José Robinson
dc.contributor.author.none.fl_str_mv Lara Guzmán, Oscar Javier
Tabares Guevara, Jorge Humberto
Sierra Restrepo, Jelver Alexander
Londoño Londoño, Julián Alberto
Álvarez Quintero, Rafael Mariano
León Varela, Yudy Milena
Osorio Durango, Edison Javier
Ramírez Pineda, José Robinson
dc.subject.none.fl_str_mv Garcinia madruno
Atherosclerosis
Biflavonoid
Foam cell
Macrophage
Morelloflavone
Oxidized LDL
Volkensiflavone
topic Garcinia madruno
Atherosclerosis
Biflavonoid
Foam cell
Macrophage
Morelloflavone
Oxidized LDL
Volkensiflavone
description ABSTARCT: The accumulation of oxidized ApoB-100-containing lipoproteins in the vascular intima and its subsequent recognition by macrophages results in foam cell formation and inflammation, key events during atherosclerosis development. Agents targeting this process are considered potentially atheroprotective. Since natural biflavonoids exert antioxidant and anti-inflammatory effects, we evaluated the atheroprotective effect of biflavonoids obtained from the tropical fruit tree Garcinia madruno. To this end, the pure biflavonoid aglycones morelloflavone (Mo) and volkensiflavone (Vo), as well as the morelloflavone's glycoside fukugiside (Fu) were tested in vitro in primary macrophages, whereas a biflavonoid fraction with defined composition (85% Mo, 10% Vo, and 5% Amentoflavone) was tested in vitro and in vivo. All biflavonoid preparations were potent reactive oxygen species (ROS) scavengers in the oxygen radical absorbance capacity assay, and most importantly, protected low-density lipoprotein particle from both lipid and protein oxidation. In biflavonoid-treated macrophages, the surface expression of the oxidized LDL (oxLDL) receptor CD36 was significantly lower than in vehicle-treated macrophages. Uptake of fluorescently labeled oxLDL and cholesterol accumulation were also attenuated in biflavonoid-treated macrophages and followed a pattern that paralleled that of CD36 surface expression. Fu and Vo inhibited oxLDL-induced ROS production and interleukin (IL)-6 secretion, respectively, whereas all aglycones, but not the glucoside Fu, inhibited the secretion of one or more of the cytokines IL-1β, IL-12p70, and monocyte chemotactic protein-1 (MCP-1) in lipopolysaccharide (LPS)-stimulated macrophages. Interestingly, in macrophages primed with low-dose LPS and stimulated with cholesterol crystals, IL-1β secretion was significantly and comparably inhibited by all biflavonoid preparations. Intraperitoneal administration of the defined biflavonoid fraction into ApoE-/- mice was atheroprotective, as evidenced by the reduction of the atheromatous lesion size and the density of T cells and macrophages infiltrating the aortic root; moreover, this treatment also lowered the circulating levels of cholesterol and the lipid peroxidation product malondialdehyde. These results reveal the potent atheroprotective effects exerted by biflavonoids on key events of the oxLDL-macrophage interphase: (i) atheroligand formation, (ii) atheroreceptor expression, (iii) foam cell transformation, and (iv) prooxidant/proinflammatory macrophage response. Furthermore, our results also evidence the antioxidant, anti-inflammatory, hypolipemiant, and atheroprotective effects of Garcinia madruno's biflavonoids in vivo.
publishDate 2017
dc.date.issued.none.fl_str_mv 2017
dc.date.accessioned.none.fl_str_mv 2019-08-13T20:00:14Z
dc.date.available.none.fl_str_mv 2019-08-13T20:00:14Z
dc.type.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.hasversion.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.local.spa.fl_str_mv Artículo de investigación
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.citation.spa.fl_str_mv Tabares-Guevara JH, Lara-Guzmán OJ, Londoño-Londoño JA, Sierra JA, León-Varela YM, Álvarez-Quintero RM, Osorio EJ, Ramirez-Pineda JR. Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo. Front Immunol. 2017 Aug 4;8:923
dc.identifier.issn.none.fl_str_mv 1664-3224
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/10495/11641
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2017.00923
identifier_str_mv Tabares-Guevara JH, Lara-Guzmán OJ, Londoño-Londoño JA, Sierra JA, León-Varela YM, Álvarez-Quintero RM, Osorio EJ, Ramirez-Pineda JR. Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo. Front Immunol. 2017 Aug 4;8:923
1664-3224
10.3389/fimmu.2017.00923
url http://hdl.handle.net/10495/11641
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Front Immunol
dc.rights.*.fl_str_mv Atribución 2.5
dc.rights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by/2.5/co/
dc.rights.accessrights.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.creativecommons.spa.fl_str_mv https://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv Atribución 2.5
http://creativecommons.org/licenses/by/2.5/co/
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 16
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Frontiers Research Foundation
dc.publisher.group.spa.fl_str_mv Grupo de Investigación en Sustancias Bioactivas (GISB)
Inmunomodulación
dc.publisher.place.spa.fl_str_mv Lausana, Suiza
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/1/TabaresGuevaraJorge_2017_BiflavonoidsModulateMacrophage.pdf
https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/2/license_url
https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/3/license_text
https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/4/license_rdf
https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/5/license.txt
bitstream.checksum.fl_str_mv 74a537c635d2bc66e974a2cd8a27205a
4afdbb8c545fd630ea7db775da747b2f
d41d8cd98f00b204e9800998ecf8427e
d41d8cd98f00b204e9800998ecf8427e
8a4605be74aa9ea9d79846c1fba20a33
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad de Antioquia
repository.mail.fl_str_mv andres.perez@udea.edu.co
_version_ 1812173082099449856
spelling Lara Guzmán, Oscar JavierTabares Guevara, Jorge HumbertoSierra Restrepo, Jelver AlexanderLondoño Londoño, Julián AlbertoÁlvarez Quintero, Rafael MarianoLeón Varela, Yudy MilenaOsorio Durango, Edison JavierRamírez Pineda, José Robinson2019-08-13T20:00:14Z2019-08-13T20:00:14Z2017Tabares-Guevara JH, Lara-Guzmán OJ, Londoño-Londoño JA, Sierra JA, León-Varela YM, Álvarez-Quintero RM, Osorio EJ, Ramirez-Pineda JR. Natural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo. Front Immunol. 2017 Aug 4;8:9231664-3224http://hdl.handle.net/10495/1164110.3389/fimmu.2017.00923ABSTARCT: The accumulation of oxidized ApoB-100-containing lipoproteins in the vascular intima and its subsequent recognition by macrophages results in foam cell formation and inflammation, key events during atherosclerosis development. Agents targeting this process are considered potentially atheroprotective. Since natural biflavonoids exert antioxidant and anti-inflammatory effects, we evaluated the atheroprotective effect of biflavonoids obtained from the tropical fruit tree Garcinia madruno. To this end, the pure biflavonoid aglycones morelloflavone (Mo) and volkensiflavone (Vo), as well as the morelloflavone's glycoside fukugiside (Fu) were tested in vitro in primary macrophages, whereas a biflavonoid fraction with defined composition (85% Mo, 10% Vo, and 5% Amentoflavone) was tested in vitro and in vivo. All biflavonoid preparations were potent reactive oxygen species (ROS) scavengers in the oxygen radical absorbance capacity assay, and most importantly, protected low-density lipoprotein particle from both lipid and protein oxidation. In biflavonoid-treated macrophages, the surface expression of the oxidized LDL (oxLDL) receptor CD36 was significantly lower than in vehicle-treated macrophages. Uptake of fluorescently labeled oxLDL and cholesterol accumulation were also attenuated in biflavonoid-treated macrophages and followed a pattern that paralleled that of CD36 surface expression. Fu and Vo inhibited oxLDL-induced ROS production and interleukin (IL)-6 secretion, respectively, whereas all aglycones, but not the glucoside Fu, inhibited the secretion of one or more of the cytokines IL-1β, IL-12p70, and monocyte chemotactic protein-1 (MCP-1) in lipopolysaccharide (LPS)-stimulated macrophages. Interestingly, in macrophages primed with low-dose LPS and stimulated with cholesterol crystals, IL-1β secretion was significantly and comparably inhibited by all biflavonoid preparations. Intraperitoneal administration of the defined biflavonoid fraction into ApoE-/- mice was atheroprotective, as evidenced by the reduction of the atheromatous lesion size and the density of T cells and macrophages infiltrating the aortic root; moreover, this treatment also lowered the circulating levels of cholesterol and the lipid peroxidation product malondialdehyde. These results reveal the potent atheroprotective effects exerted by biflavonoids on key events of the oxLDL-macrophage interphase: (i) atheroligand formation, (ii) atheroreceptor expression, (iii) foam cell transformation, and (iv) prooxidant/proinflammatory macrophage response. Furthermore, our results also evidence the antioxidant, anti-inflammatory, hypolipemiant, and atheroprotective effects of Garcinia madruno's biflavonoids in vivo.16application/pdfengFrontiers Research FoundationGrupo de Investigación en Sustancias Bioactivas (GISB)InmunomodulaciónLausana, Suizainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85Atribución 2.5info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by/4.0/Garcinia madrunoAtherosclerosisBiflavonoidFoam cellMacrophageMorelloflavoneOxidized LDLVolkensiflavoneNatural Biflavonoids Modulate Macrophage-Oxidized LDL Interaction In Vitro and Promote Atheroprotection In VivoFront ImmunolFrontiers in Immunology11784ORIGINALTabaresGuevaraJorge_2017_BiflavonoidsModulateMacrophage.pdfTabaresGuevaraJorge_2017_BiflavonoidsModulateMacrophage.pdfArtículo de investigaciónapplication/pdf1882404https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/1/TabaresGuevaraJorge_2017_BiflavonoidsModulateMacrophage.pdf74a537c635d2bc66e974a2cd8a27205aMD51CC-LICENSElicense_urllicense_urltext/plain; charset=utf-849https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/2/license_url4afdbb8c545fd630ea7db775da747b2fMD52license_textlicense_texttext/html; charset=utf-80https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/3/license_textd41d8cd98f00b204e9800998ecf8427eMD53license_rdflicense_rdfLicenciaapplication/rdf+xml; charset=utf-80https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/4/license_rdfd41d8cd98f00b204e9800998ecf8427eMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstream/10495/11641/5/license.txt8a4605be74aa9ea9d79846c1fba20a33MD5510495/11641oai:bibliotecadigital.udea.edu.co:10495/116412022-12-20 23:39:51.72Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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