(−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation

Abstract

The antioxidant and anti-inflammatory responses of (−)-methyl-oleocanthal (met-OLE), a new metabolite of the extra virgin olive oil (EVOO) phenolic oleocanthal (OLE), were explored in lipopolysaccharide (LPS)-induced murine peritoneal macrophages. Possible signaling pathways and epigenetic modulation of histones were studied. Met-OLE inhibited LPS-induced intracellular reactive oxygen species (ROS) and nitrite (NO) production and decreased the overexpression of the pro-inflammatory enzymes COX-2, mPGES-1 and iNOS in murine macrophages. In addition, met-OLE was able to significantly decrease the activation of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs) and blocked canonical and non-canonical inflammasome signaling pathways. On the contrary, met-OLE upregulated haem oxigenase 1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) expression in treated cells. Finally, met-OLE pretreated spleen cells counteracted LPS induction, preventing H3K18 acetylation or H3K9 and H3K27 demethylation. Overall, these results provide novel mechanistic insights into the beneficial effects of met-OLE regarding the regulation of the immune–inflammatory response through epigenetic changes in histone markers. This revealing evidence suggests that the methylated metabolite of OLE may contribute significantly to the beneficial effects that are associated with the secoiridoid-related compound and the usual consumption of EVOO.

Dietary oleacein, a secoiridoid from extra virgin olive oil, prevents collagen-induced arthritis in mice

“…Procopio's group later improved the conversion of oleuropein changing DMSO by water and heating in a microwave reactor, with the presence of inorganic salts, to get OLA in just 20 minutes with a 48% yield. 25 For that time, we were also working in the improvement of the semisynthesis of OLA from oleuropein, and that of oleocanthal from ligustroside, 10 following the recommendations of a previous work aimed at adapting the classical Krapcho decarboxylation experimental conditions to an aqueous microwave scenario. 26 As a result, we changed DMSO by water, and we decided not adding inorganic salts in one of our assays, finding that the reaction of semi-synthesis of OLA from oleuropein worked properly.…”

“…Other reagents, solvents, material, and instruments used in this work were previously described. 10 A mixture of (-)-oleuropein (0.40 g) and H 2 O (25 mL) was subjected to microwave irradiation for 13 minutes at 180 °C. The resulting crude reaction was extracted with CHCl 3 (3 × 30 mL).…”

“…In this context, in the last decade, our research group has demonstrated the therapeutic effects of dietary supplementation with EVOO 8 and some of its bioactive compounds in a collagen-induced arthritis (CIA) in mice. [8][9][10] This animal model is one of the most widely used to study and evaluate key RA pathogenic mechanisms and novel antiarthritic drugs. It is defined by the production of CII-specific antibodies, a hallmark also described in RA.…”

Rich Oleocanthal and Oleacein Extra Virgin Olive Oil and Inflammatory and Antioxidant Status in people with Obesity and Prediabetes. The APRIL Study: a Randomised, Controlled Crossover Study

“…Therefore, one-month intervention with EVOO promoted a healthier oxidative profile than OO in obese people with prediabetes. The bioactive compounds involved in these beneficial effects of EVOO could be the complex polyphenols, especially oleocanthal and oleacein which have been demonstrated to elicit some antioxidant effects in in vitro and in vivo assays [26][27][28][29][30] and constitute 90% of total polyphenol content in this EVOO. However, a contribution of other minor complex polyphenols such as oleuropein, ligstroside as well as lignans and flavonoids, at least partially, cannot be ruled out.…”

Oleocanthal, an Antioxidant Phenolic Compound in Extra Virgin Olive Oil (EVOO): A Comprehensive Systematic Review of Its Potential in Inflammation and Cancer

“…These effects have been described to be related with the inhibition of ROS production, MAPKs, and the inflammasome cascade signaling pathway (Figure 4) [30]. In the pursuit of novel strategies to enhance the effectiveness of OC, Montoya and colleagues introduced a methylated derivative of OC, known as (-)-Methyl-oleocanthal (metOC) [31]. This compound has also demonstrated antioxidant and anti-inflammatory properties when tested on murine macrophages stimulated by LPS.…”