Melissa officinalis essential oil reduces plasma triglyceride levels by downregulating SREBP‐1c expression and the epigenetic modifications on SREBP‐1c target genes

Abstract

We investigated hypolipidemic mechanism of Melissa officinalis essential oil (MOEO). The major compound in MOEO was geranial (65%, w/w), quantified with GC/MS. After 2‐week feeding (0.0125 mg MOEO/mouse/day), plasma triglyceride levels were significantly reduced (−32%, P<0.05) in human apoE2 transgenic mice. Mouse hepatic transcriptome profiling with oligonucleotide microarray showed that fatty acid synthesis and β‐oxidation pathways were significantly altered. The rate of β‐oxidation, quantified with [1‐14C]palmitate, was not changed with MOEO in HepG2 cells, however, the expressions of SREBP‐1c and its target genes in the fatty acid synthesis including ACC2, FAS, and SCD1 were reduced in mouse livers assessed by quantitative PCR. The nuclear SREBP‐1c was reduced as well (−30%, P<.05). Chromatin immunoprecipitation results suggested that the bindings of PCAF, a coactivator of SREBP‐1c, and its H3K14 acetylation on the promoter of ACC2 (−9% for H3K14ac and −21% for PCAF binding) and FAS (−37% for H3K14ac and −10% for PCAF) were reduced. These suggest that MOEO may reduce plasma triglyceride levels by multiple mechanisms. The reduction of SREBP‐1c and its target gene expressions, decreasing nuclear translocation of SREBP‐1c, and the epigenetic down‐regulation of genes in fatty acid synthesis may result in net hypotriglyceridemic effects.