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...
- 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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 |