Health benefits of Olive Leaf Extract: Analysis of health benefits of Olive Leaf Extract using in vivo transcriptomic profiling

Abstract

Olive Leaf Extract (OLE) has been used for many of years to benefit human health, but investigation of the scientific basis of these effects is relatively recent. OLE polyphenols have shown therapeutic effects on a wide range of ailments including cardiovascular disease, diabetes and cancer. Although recent literature has described a link between these ailments and a protective effect of OLE, the mode of action is less clear. Genes that respond to OLE were investigated to determine underlying mechanisms that correlate to health benefits. A double blind placebo (PBO) controlled trial design was performed. Gene expression profiles of peripheral blood mononuclear cells (PBMCs) from healthy male volunteers (n=29) were analysed using RNA samples for Affymetrix arrays following an 8-week intervention with a 20ml daily consumption of either OLE or PBO. The difference between groups was determined using an adjusted linear model. Analysis of the human samples indicated a down-regulation of genes important in inflammatory pathways, lipid metabolism and cancer with OLE. Gene expression was verified by real-time-PCR for three genes (EGR1, COX-2 and ID3). Further investigation was carried out using in vitro cell models to determine the inflammatory pathways utilised by OLE. Nucleotide-binding oligomerization domain-containing protein (NOD)2-WT, NOD2-G908R, Human Embryonic Kidney 293 (HEK)Blue™-2 and HEKBlue™-4 cells were analysed for inflammatory response to OLE. These models demonstrated OLE interacts with both intracellular and membrane bound receptors to downregulate inflammatory pathways. Lastly the apoptosis/ proliferation effects of OLE in cancer models were investigated. OLE had an inhibitory effect in MCF-7 (breast) and LNCaP (prostate) cancer cell lines. A 70% survival with OLE treatment was used for real-time-PCR analysis to measure differential gene expression. Gene expression suggests an anti-inflammatory effect could be inhibiting cancer cell proliferation. The results presented here support a gene expression level manipulation by OLE creating health benefits to humans through effects on inflammatory and metabolic pathways. Future studies with a larger study group, including both male and female participants, looking into direct effects of lipid metabolism and reduced inflammation are warranted.