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

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Lipids

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.

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Abbreviations

C:

Cholesterol

CE:

Cholesteryl esters

ChoGpl:

Choline glycerophospholipids

EOs:

Essential oils

EtnGpl:

Ethanolamine glycerophospholipids

HMGCR:

3-Hydroxy-3-methylglutaryl-coenzyme A reductase

LaEO:

Lippia alba essential oil

LaEOca:

Lippia alba essential oil carvone chemotype

LaEOci:

Lippia alba essential oil citral chemotype

LaEOpi:

Lippia alba essential oil piperitone chemotype

LaEOta:

Lippia alba essential oil tagetenone chemotype

LD:

Lipid droplet

PL:

Phospholipids

PtdSer:

Phosphatidylserines

TAG:

Triacylglycerols

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Acknowledgements

This work was supported by research Grants from the Consejo Nacional de Investigaciones Científicas y Técnicas Argentina, the Agencia Nacional de Promoción Científica y Tecnológica, and the Universidad Nacional de La Plata. We would like to thank José Cicció-Alberti, CIPRONA, Universidad de Costa Rica, for kindly supplied the essential oils of Lippia alba. We are also grateful to Dr. Donald F. Haggerty, a retired academic career investigator and native English speaker, for editing the final version of the manuscript.

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Authors and Affiliations

  1. INIBIOLP “Prof. Dr. Rodolfo R. Brenner” (CONICET-CCT La Plata), Facultad Ciencias Médicas, UNLP, Calles 60 y 120, La Plata, Argentina

    Sandra Montero-Villegas, Mónica Polo, Marianela Galle, Boris Rodenak-Kladniew, María Castro, Ana Ves-Losada, Rosana Crespo & Margarita García de Bravo

  2. Dto de Cs. Biológicas, Facultad de Cs Exactas, UNLP, La Plata, Argentina

    Ana Ves-Losada

Authors
  1. Sandra Montero-Villegas
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  2. Mónica Polo
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  3. Marianela Galle
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  4. Boris Rodenak-Kladniew
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  5. María Castro
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  6. Ana Ves-Losada
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  7. Rosana Crespo
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  8. Margarita García de Bravo
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Correspondence to Rosana Crespo.

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Montero-Villegas, S., Polo, M., Galle, M. et al. Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by Lippia alba Essential Oils. Lipids 52, 37–49 (2017). https://doi.org/10.1007/s11745-016-4218-x

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