Lavender Essential Oil Modulates Hepatic Cholesterol Metabolism in HepG2 Cells

Cholesterol is an essential lipid that guarantees several biological processes in eukaryotic cells. Its metabolism is regulated by a complex protein network that could be significantly influenced by numerous exogenous sources, such as essential oils (EOs). For instance, it has been speculated that monoterpenoid and sesquiterpenoid compounds contained in lavender essential oil (LEO) may exert important hypocholesterolemic activities. However, the molecular mechanisms by which LEO influences cholesterol homeostasis are not characterized. In this work, we evaluated the ability of LEO to regulate the protein network that controls cholesterol metabolism in the HepG2 cell line. The main findings indicate that LEO administration increases intracellular cholesterol content. Concurrently, LEO affects the expression of proteins involved in cholesterol uptake, biosynthesis, and trafficking. These effects are partially mediated by terpinene-4-ol, one of the most abundant compounds in LEO. These results demonstrate that LEO modulates cholesterol metabolism in hepatic cells.

[1]  Tianyu Yang,et al.  The Role of Tea Tree Oil in Alleviating Palmitic Acid-Induced Lipid Accumulation in Bovine Hepatocytes , 2022, Frontiers in Veterinary Science.

[2]  G. Saviano,et al.  Chemical Profile, In Vitro Biological Activity and Comparison of Essential Oils from Fresh and Dried Flowers of Lavandula angustifolia L. , 2021, Molecules.

[3]  B. Brügger,et al.  Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme SQS , 2021, bioRxiv.

[4]  S. Di Bartolomeo,et al.  Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis , 2021, International journal of molecular sciences.

[5]  Damian Rodriguez,et al.  Cholesterol‐lowering activity of natural mono‐ and sesquiterpenoid compounds in essential oils: A review and investigation of mechanisms using in silico protein–ligand docking , 2021, Phytotherapy research : PTR.

[6]  F. Pfrieger,et al.  Understanding and Treating Niemann–Pick Type C Disease: Models Matter , 2020, International journal of molecular sciences.

[7]  J. Nathan.  Squalene and cholesterol in the balance at the ER membrane , 2020, Proceedings of the National Academy of Sciences.

[8]  R. Krauss,et al.  Phosphatidylinositol-(4,5)-Bisphosphate Regulates Plasma Cholesterol Through LDL (Low-Density Lipoprotein) Receptor Lysosomal Degradation , 2020, Arteriosclerosis, thrombosis, and vascular biology.

[9]  S. Di Bartolomeo,et al.  Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins by JQ1 Unravels a Novel Epigenetic Modulation to Control Lipid Homeostasis , 2020, International journal of molecular sciences.

[10]  J. Goldstein,et al.  Retrospective on Cholesterol Homeostasis: The Central Role of Scap. , 2018, Annual review of biochemistry.

[11]  F. Kraemer,et al.  SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux. , 2018, Annual review of physiology.

[12]  P. R. Naik,et al.  Ameliorative effect of borneol, a natural bicyclic monoterpene against hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic Wistar rats. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[13]  S. Hatakeyama,et al.  Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival , 2017, Nature Communications.

[14]  Bhavani Nagarajan,et al.  Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging , 2016, Front. Pharmacol..

[15]  M. Segatto,et al.  Cholesterol Homeostasis Imbalance and Brain Functioning: Neurological Disorders and Behavioral Consequences , 2014 .

[16]  M. Rafieian-kopaei,et al.  Effect of Dietary Ethanolic Extract of Lavandula officinalis on Serum Lipids Profile in Rats , 2014, Iranian journal of pharmaceutical research : IJPR.

[17]  K. Kim,et al.  Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome[S] , 2014, Journal of Lipid Research.

[18]  M. Poirot,et al.  Cholesterol and Cancer, in the Balance , 2014, Science.

[19]  U. Eriksson,et al.  Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease , 2013, Nature Protocols.

[20]  M. Nowaczyk,et al.  Smith–Lemli–Opitz syndrome: Phenotype, natural history, and epidemiology , 2012, American journal of medical genetics. Part C, Seminars in medical genetics.

[21]  V. Pallottini,et al.  Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic "power station". , 2012, World journal of hepatology.

[22]  P. Ascenzi,et al.  Potential role of nonstatin cholesterol lowering agents , 2011, IUBMB life.

[23]  K. Kim,et al.  Linalool reduces the expression of 3‐hydroxy‐3‐methylglutaryl CoA reductase via sterol regulatory element binding protein‐2‐ and ubiquitin‐dependent mechanisms , 2011, FEBS letters.

[24]  Ikumi Chisaki,et al.  Regulation mechanism of ABCA1 expression by statins in hepatocytes. , 2011, European journal of pharmacology.

[25]  E. Kang,et al.  Up-regulation of hepatic low-density lipoprotein receptor-related protein 1: a possible novel mechanism of antiatherogenic activity of hydroxymethylglutaryl-coenzyme A reductase inhibitor Atorvastatin and hepatic LRP1 expression. , 2011, Metabolism: clinical and experimental.

[26]  R. DeBose-Boyd.  Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase , 2008, Cell Research.

[27]  K. Kim,et al.  Asian plantain (Plantago asiatica) essential oils suppress 3-hydroxy-3-methyl-glutaryl-co-enzyme A reductase expression in vitro and in vivo and show hypocholesterolaemic properties in mice , 2007, British Journal of Nutrition.

[28]  L. Schurgers,et al.  Glia‐induced neuronal differentiation by transcriptional regulation , 2007, Glia.

[29]  R. Adams,et al.  Identification of Essential Oil Components By Gas Chromatography/Mass Spectrometry , 2007 .

[30]  Andrew J. Brown,et al.  SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR. , 2006, The Biochemical journal.

[31]  J. Pasqualini.  Enzymes involved in the formation and transformation of steroid hormones in the fetal and placental compartments , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[32]  M. Kaiser,et al.  Qualitative and Quantitative Analysis by Gas Chromatography , 2004 .

[33]  Jonathan C. Cohen,et al.  ABCG5 and ABCG8 Are Obligate Heterodimers for Protein Trafficking and Biliary Cholesterol Excretion* , 2003, Journal of Biological Chemistry.

[34]  P. Hart,et al.  Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes , 2000, Inflammation Research.

[35]  J. Goldstein,et al.  The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor , 1997, Cell.

[36]  Robert L. Grob,et al.  Modern Practice of Gas Chromatography , 1995 .

[37]  T. Osborne,et al.  Cooperation by Sterol Regulatory Element-binding Protein and Sp1 in Sterol Regulation of Low Density Lipoprotein Receptor Gene (*) , 1995, The Journal of Biological Chemistry.

[38]  H. Ginsberg,et al.  Hepatic Synthesis of Lipoproteins and Apolipoproteins , 1992, Seminars in liver disease.

[39]  N. Javitt.  Hep G2 cells as a resource for metabolic studies: lipoprotein, cholesterol, and bile acids , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  T. Tansey,et al.  Squalene synthase: structure and regulation. , 2001, Progress in nucleic acid research and molecular biology.

[41]  H. Vandendool,et al.  A GENERALIZATION OF THE RETENTION INDEX SYSTEM INCLUDING LINEAR TEMPERATURE PROGRAMMED GAS-LIQUID PARTITION CHROMATOGRAPHY. , 1963, Journal of chromatography.