Human Intervention Study to Assess the Effects of Supplementation with Olive Leaf Extract on Peripheral Blood Mononuclear Cell Gene Expression

Abstract

Olive leaf extract (OLE) has been used for many years for its putative health benefits, but, to date, scientific evidence for the basis of these effects has been weak. Although recent literature has described a link between ailments such as cardiovascular disease, diabetes and cancer and a protective effect of polyphenols in the OLE, the mode of action is still unclear. Here, we describe a double-blinded placebo (PBO)-controlled trial, in which gene expression profiles of peripheral blood mononuclear cells from healthy male volunteers (n = 29) were analysed to identify genes that responded to OLE, following an eight-week intervention with 20 mL daily consumption of either OLE or PBO. Differences between groups were determined using an adjusted linear model. Subsequent analyses indicated downregulation of genes important in inflammatory pathways, lipid metabolism and cancer as a result of OLE consumption. Gene expression was verified by real-time PCR for three genes (EGR1, COX-2 and ID3). The results presented here suggest that OLE consumption may result in health benefits through influencing the expression of genes in inflammatory and metabolic pathways. Future studies with a larger study group, including male and female participants, looking into direct effects of OLE on lipid metabolism and inflammation are warranted.

Olive Leaf (<b><i>Olea europaea L. folium</i></b>): Potential Effects on Glycemia and Lipidemia

“…Potential effects of olive leaf on lipid metabolism and inflammation emerge by means of metabolic pathways and inflammationrelated genes [13,[47][48][49][50]. In a study supporting these results, it was found that daily 20 mL olive leaf extract supplementation given to 29 healthy male participants changed expression level of early growth response protein 1, cyclooxygenase-2, and inhibitor of DNA binding 3 genes in peripheral blood mononuclear cells [47]. A study conducted with ovariectomized rats showed that olive leaf extract supplementation at the doses of 200 or 400 mg/kg body weight decreased serum triglyceride level particularly at high doses [48].…”

Critical Evaluation of Gene Expression Changes in Human Tissues in Response to Supplementation with Dietary Bioactive Compounds: Moving Towards Better-Quality Studies

“…This type of studies deserves a complete separate revision. After we excluded some manuscripts reporting only microarray results, we revised and compiled information from 75 human intervention trials published between 1994 and 2018 ( supplementary Table S1 ) [ 4 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ,…”

“…Of those studies that included information about the RNA quality, two of them only mentioned that some of the samples had low quality [ 15 , 82 ] and four studies reported the quality of the ARN based solely on the Abs 260/280 with values between 1.8 and 2.1 [ 37 , 67 , 74 , 75 ]. Two studies reported the RNA integrity number (RIN) values of their samples, RIN > 8.0 [ 64 ] and RIN = 6–9 [ 54 ], respectively, and only two other studies combined Abs 260/280 and RIN values [ 4 , 51 ] to prove the quality of their RNA samples.…”

“…Only a few studies indicated to have used the average value or the combination of various reference genes ( GAPDH , ACTB , HPRT1 , B2M ) [ 18 , 40 ], ( GAPDH , ACTB ) [ 64 ] and ( ACTB , UBC , PPIA ) [ 58 ] for the normalization process whereas others reported to have used separate reference genes ( RPLP0 , ACTB , B2M ) [ 82 ] and ( GAPDH , HMBS ) [ 45 ] for the analysis of expression changes of different target genes within the same study. A total of seven studies did not clearly report the use of or the specific reference gene employed in their analyses.…”

Optimization of Ultrasonic-Assisted Extraction of Major Phenolic Compounds from Olive Leaves (Olea europaea L.) Using Response Surface Methodology

“…Those bioactive compounds display various effects on human health, primarily as antioxidants and activators of gene expression, as well as displaying an effect on healthy gut microbiota and maintaining the efficacy of the mitochondria [ 8 , 9 , 10 ]. For these reasons, they are used in the production of natural pharmaceutical supplements, as well as additives for the food and cosmetic industries [ 11 ].…”