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). [C]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 [C]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.

Cholesterol‐lowering activity of natural mono‐ and sesquiterpenoid compounds in essential oils: A review and investigation of mechanisms using in silico protein–ligand docking

“…This also suggests that Lippia alba EO may not have the same side effects associated with statins. The myrcenone/tangentone chemotype of the EO was most effective in lowering HMGCR levels, TGs, cholesterol, and phospholipid synthesis (Montero‐Villegas et al, 2017).…”

Essential Oils and Factors Related to Cardiovascular Diseases

“…Treatment of human hepatoma (HepG2) cells with Pinus koraiensis essential oil suppressed the expression of lipid-related genes, such as SREBP-1c, SREBP-2, HMGCR, fatty acid synthase, and glycerol-3-phosphate acyltransferase, increased the expression of low density lipoprotein receptors and inhibited the activation of human acyl-coenzyme A: cholesterol acyltransferases (hACAT) 1 and 2 [47]. Treatment of HepG2 cells with Lippia alba essential oil, especially the tagetenone chemotype, decreased lipid synthesis, lipid contents, and volume of lipid droplets via the mevalonate pathway [35]. Also, incubation of HepG2 cells with Artemisia princeps essential oil significantly increased LDL-R expression [21].…”

New Chemovariety ofLippia albaFrom Colombia: Compositional Analysis of the Volatile Secondary Metabolites and Somein vitroBiological Activities of the Essential Oil From Plant Leaves

“…When these compositions were compared with the revised literature on the chemistry of L. alba EO, 3 -25 any report mentioning an EO with high content of cis -piperitone oxide (>10%) was not found; this molecule was always reported as an absent or minor/trace component (~0%-1%). Nonetheless, limonene and germacrene D have often been described as abundant (~9%-51%).…”

“…1 In the northern region of Colombia, this plant is commonly called “oreganito, orégano de cerro, curalotodo, or pronto alivio,” and it is prepared as infusions or tinctures to treat colds and digestive problems, and for fever relief. 2 In accordance with the reviewed scientific literature, there are 32 chemovar (ie, type/subtype) known for the essential oils (EOs) from L. alba , which are represented by one or combination of constituents as bicyclosesquiphellandrene, camphor, carvone, β-caryophyllene, caryophyllene oxide, citral, citrol, dihydrocarvone, estragole, eucalyptol, germacrene D, α-guaiene, limonene, linalool, lippione, myrcene, myrcenone, E/Z-β-ocimene, ocimenone, piperitone, and γ-terpinene, 1,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25 in relative amounts ranging between ~10% and 91% and EO yields around ~0.1% to 3.2%. For Colombia, 4 chemovar were previously reported.…”