Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

Abstract

Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols.

Mediterranean diet and health status: Active ingredients and pharmacological mechanisms

“…oleuropein, or oleocanthal (Rigacci, ). In a mouse model of 2,6,10,14‐tetramethylpentadecan‐induced systemic lupus erythematosus, application of phenol‐enriched EVOO led to a decrease in kidney damage along with reduced renal levels of MMP3 and PGE 2 (Menicacci, Cipriani, Margheri, Mocali, & Giovannelli, ). Furthermore, incubation of peripheral blood mononuclear cells harvested from systemic lupus erythematosus patients with a phenolic fraction of EVOO resulted in a reduced synthesis of the pro‐inflammatory cytokines TNF‐α, IL‐1β, and IL‐6 with concomitant increase in IL‐10 production (Aparicio‐Soto et al, ).…”

Pharma-Nutritional Properties of Olive Oil Phenols. Transfer of New Findings to Human Nutrition

“…In NHDF, OLE and HT treatment counteracted senescence-related rises in COX-2 expression, NF-κB protein level, and nuclear localization. In addition, pre-treatment with these phenolic compounds prevented TNF-α-induced inflammatory effects in these cells [ 181 ].…”

Extra-Virgin Olive Oil from Apulian Cultivars and Intestinal Inflammation

“…Oleuropein, responsible for the bitter taste of the oil, is a bioactive secoiridoid particularly abundant in green olive drupes [36]. Oleuropein is able to modulate senescence-associated inflammatory phenotype, via the downregulation of senescence/inflammation markers such as interleukin-6 (IL-6), metalloprotease secretion and COX-2 [37]. Ex vivo treatment with oleuropein of colonic biopsy from patients with colitis, decreases the expression of IL-17 and COX-2, thus resulting in the amelioration of the inflammatory process [38].…”