Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils

Autores
Montero Villegas, Sandra; Polo, Mónica Patricia; Galle, Marianela; Rodenak Kladniew, Boris Emilio; Castro, María Cecilia; Ves Losada, Ana; Crespo, Rosana; García de Bravo, Margarita María
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L.alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [¹⁴C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2–32 µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [¹⁴C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic L.alba EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that L.alba EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases.
Instituto de Investigaciones Bioquímicas de La Plata
Facultad de Ciencias Exactas
Materia
Medicina
Ciencias Exactas
Lippia alba
Essential oil
Cholesterogenesis
Lipid droplets
Culture cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/137671

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network_name_str SEDICI (UNLP)
spelling Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential OilsMontero Villegas, SandraPolo, Mónica PatriciaGalle, MarianelaRodenak Kladniew, Boris EmilioCastro, María CeciliaVes Losada, AnaCrespo, RosanaGarcía de Bravo, Margarita MaríaMedicinaCiencias ExactasLippia albaEssential oilCholesterogenesisLipid dropletsCulture cellsThe essential oils (EOs) of <i>Lippia alba</i>, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that <i>L.alba</i> EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four <i>L.alba</i> chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [¹⁴C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2–32 µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [¹⁴C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic <i>L.alba</i> EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that <i>L.alba</i> EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Exactas2017-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf37-49http://sedici.unlp.edu.ar/handle/10915/137671enginfo:eu-repo/semantics/altIdentifier/issn/1558-9307info:eu-repo/semantics/altIdentifier/issn/0024-4201info:eu-repo/semantics/altIdentifier/doi/10.1007/s11745-016-4218-xinfo:eu-repo/semantics/altIdentifier/pmid/27905068info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-11-26T10:09:59Zoai:sedici.unlp.edu.ar:10915/137671Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-11-26 10:09:59.974SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
title Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
spellingShingle Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
Montero Villegas, Sandra
Medicina
Ciencias Exactas
Lippia alba
Essential oil
Cholesterogenesis
Lipid droplets
Culture cells
title_short Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
title_full Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
title_fullStr Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
title_full_unstemmed Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
title_sort Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by <i>Lippia alba</i> Essential Oils
dc.creator.none.fl_str_mv Montero Villegas, Sandra
Polo, Mónica Patricia
Galle, Marianela
Rodenak Kladniew, Boris Emilio
Castro, María Cecilia
Ves Losada, Ana
Crespo, Rosana
García de Bravo, Margarita María
author Montero Villegas, Sandra
author_facet Montero Villegas, Sandra
Polo, Mónica Patricia
Galle, Marianela
Rodenak Kladniew, Boris Emilio
Castro, María Cecilia
Ves Losada, Ana
Crespo, Rosana
García de Bravo, Margarita María
author_role author
author2 Polo, Mónica Patricia
Galle, Marianela
Rodenak Kladniew, Boris Emilio
Castro, María Cecilia
Ves Losada, Ana
Crespo, Rosana
García de Bravo, Margarita María
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Medicina
Ciencias Exactas
Lippia alba
Essential oil
Cholesterogenesis
Lipid droplets
Culture cells
topic Medicina
Ciencias Exactas
Lippia alba
Essential oil
Cholesterogenesis
Lipid droplets
Culture cells
dc.description.none.fl_txt_mv The essential oils (EOs) of <i>Lippia alba</i>, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that <i>L.alba</i> EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four <i>L.alba</i> chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [¹⁴C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2–32 µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [¹⁴C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic <i>L.alba</i> EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that <i>L.alba</i> EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases.
Instituto de Investigaciones Bioquímicas de La Plata
Facultad de Ciencias Exactas
description The essential oils (EOs) of <i>Lippia alba</i>, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that <i>L.alba</i> EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four <i>L.alba</i> chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [¹⁴C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2–32 µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [¹⁴C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic <i>L.alba</i> EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that <i>L.alba</i> EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases.
publishDate 2017
dc.date.none.fl_str_mv 2017-01
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info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
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dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/issn/0024-4201
info:eu-repo/semantics/altIdentifier/doi/10.1007/s11745-016-4218-x
info:eu-repo/semantics/altIdentifier/pmid/27905068
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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