title: Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by Lippia alba Essential Oils.
abstract: 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.
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina.
authors.forename: Sandra
authors.initials: S
authors.lastname: Montero-Villegas
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina.
authors.forename: Mónica
authors.initials: M
authors.lastname: Polo
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina.
authors.forename: Marianela
authors.initials: M
authors.lastname: Galle
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina.
authors.forename: Boris
authors.initials: B
authors.lastname: Rodenak-Kladniew
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina.
authors.forename: María
authors.initials: M
authors.lastname: Castro
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina.|Dto de Cs. Biológicas, Facultad de Cs Exactas, UNLP, La Plata, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Ves-Losada
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina. rcrespo@med.unlp.edu.ar.
authors.forename: Rosana
authors.initials: R
authors.lastname: Crespo
authors.affiliation: INIBIOLP "Prof. Dr. Rodolfo R. Brenner" (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina.
authors.forename: Margarita
authors.initials: M
authors.lastname: García de Bravo
mesh_terms: D000072283:A549 Cells; D053898:Biosynthetic Pathways / Q000187:drug effects*; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis; D056945:Hep G2 Cells; D006801:Humans; D032411:Lippia / Q000737:chemistry*; D008798:Mevalonic Acid / Q000378:metabolism*; D009822:Oils, Volatile / Q000494:pharmacology*; D010938:Plant Oils / Q000494:pharmacology; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D009822:Oils, Volatile; D010938:Plant Oils; D014280:Triglycerides; D002784:Cholesterol; D008798:Mevalonic Acid
keywords: Cholesterogenesis; Culture cells; Essential oil; Lipid droplets; Lippia alba