Anti-Inflammatory Effects of Nutritionally Relevant Concentrations of Oleuropein and Hydroxytyrosol on Peripheral Blood Mononuclear Cells: An Age-Related Analysis

Abstract

Immunosenescence and inflammaging facilitate the insurgence of chronic diseases. The Mediterranean diet is a non-invasive intervention to improve the chronic low-grade inflammatory status associated with aging. Olive oil oleuropein (OLE) and hydroxytyrosol (HT) demonstrated a controversial modulatory action on inflammation in vitro when tested at concentrations exceeding those detectable in human plasma. We studied the potential anti-inflammatory effects of OLE and HT at nutritionally relevant concentrations on peripheral blood mononuclear cells (PBMCs) as regards cell viability, frequency of leukocyte subsets, and cytokine release, performing an age-focused analysis on two groups of subjects: Adult (age 18–64 years) and Senior (age ≥ 65 years). OLE and HT were used alone or as a pre-treatment before challenging PBMCs with lipopolysaccharide (LPS). Both polyphenols had no effect on cell viability irrespective of LPS, but 5 µM HT had an LPS-like effect on monocytes, reducing the intermediate subset in Adult subjects. OLE and HT had no effect on LPS-triggered release of TNF-α, IL-6 and IL-8, but 5 µM HT reduced IL-10 secretion by PBMCs from Adult vs. Senior group. In summary, nutritionally relevant concentrations of OLE and HT elicit no anti-inflammatory effect and influence the frequency of immune cell subsets with age-related different outcomes.

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

“…However, even at high concentrations, OLE and HT seem to be selectively cytotoxic for cancer cells, with no or negligible/minimal effects on non-cancer cells, as demonstrated for embryonic rat cardiomyoblasts H9c2(2-1), human breast epithelial cell line MCF-10A [ 41 , 93 ], nonmalignant human bronchial epithelial BEAS-2B cell line [ 35 ], normal colonic cell line CCD-841CoN [ 74 ], human normal liver cell line (HL-7702) [ 67 ], human normal prostate epithelial cells PWLE2 [ 86 ], human bile duct cell line HIBEpiC [ 69 ], human fibroblasts WI-38 [ 90 ], normal skin fibroblast cell line WS1 [ 74 ], human GN61 gingival fibroblasts [ 271 ], human lymphocytes [ 78 ], human PBMCs [ 24 , 25 ], and normal human fibroblasts [ 272 , 273 ]. Thus, OLE and HT are generally considered safe on the basis of experimental data, despite sporadic reports against the trend, as happened for HT, which proved to be toxic for human non-tumorigenic pancreas cells HPDE [ 80 ] and human normal prostate RWPE-1 cells [ 87 ].…”

“…Chemotherapy may also account for an exacerbation of inflammation, whose biological meaning is poorly understood, being recognized as immune-activating as well as a contributor to the failure of the therapeutic regimen [ 303 , 304 , 305 ]. OLE and HT exhibit an anti-inflammatory activity that has been demonstrated in multiple in vivo and in vitro models, although some experimental variables related to the timing of administration of inflammatory stimuli might have affected the reproducibility of the results, mainly in vitro, and nutritionally relevant concentrations of OLE and HT often showed no anti-inflammatory activity on human peripheral blood mononuclear cells [ 24 , 25 ].…”

“…Both compounds have attracted attention for their accessibility, safe profile, powerful antioxidant and scavenging activity against reactive oxygen species (ROS), and controversial anti-inflammatory action. For more than two decades, OLE and HT (together or alone) have been the focus of intense research efforts in the context of infectious diseases and prevention/management of chronic non-communicable diseases, including cancer, with encouraging results from in vitro and in vivo models [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”