Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae and Pedialaceae, among others. Specifically, Olea europaea L. (Oleaceae) is rich in oleuropein (OL), dimethyl-OL, and ligstroside secoiridoids, and their hydrolysis derivatives are mostly OL-aglycone, oleocanthal (OLE), oleacein (OLA), elenolate, oleoside-11-methyl ester, elenoic acid, hydroxytyrosol (HTy), and tyrosol (Ty). These compounds have proved their efficacy in the management of diabetes, cardiovascular and neurodegenerative disorders, cancer, and viral and microbial infections. Particularly, the antioxidant, anti-inflammatory, and immunomodulatory properties of secoiridoids from the olive tree (Olea europaea L. (Oleaceae)) have been suggested as a potential application in a large number of inflammatory and reactive oxygen species (ROS)-mediated diseases. Thus, the purpose of this review is to summarize recent advances in the protective role of secoiridoids derived from the olive tree (preclinical studies and clinical trials) in diseases with an important pathogenic contribution of oxidative and peroxidative stress and damage, focusing on their plausible mechanisms of the action involved.

The present study was designed to investigate the role of the canonical and noncanonical inflammasome, MAPKs and NRF-2/HO-1, signaling pathways involved in the antioxidant and anti-inflammatory activities of oleocanthal in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Isolated cells were treated with oleocanthal in the presence or absence of LPS (5 μg mL–1) for 18 h. Oleocanthal showed a potent reduction of reactive oxygen species (ROS) (25 μM, 50. 612 ± 0.02; 50 μM, 53. 665 ± 0.09; 100 μM, 52. 839 ± 0.02), nitrites (25 μM, 0.631 ± 0.07; 50 μM, 0.652 ± 0.07; 100 μM, 0.711 ± 0.08), and pro-inflammatory cytokines levels when compared with LPS–DMSO-treated control cells. In terms of enzymes protein expression, oleocanthal was able to downregulate iNOS (25 μM, 0.173 ± 0.02; 50 μM, 0.149 ± 0.01; 100 μM, 0.150 ± 0.01;p < 0.001), COX-2 (25 μM, 0.482 ± 0.08; 50 μM, 0.469 ± 0.05; 100 μM, 0.418 ± 0.06; p < 0.001), and mPGES-1 (25 μM, 0.185 ± 0.11; 50 μM, 0.218 ± 0.13; 100 μM, 0.161 ± 0.15; p < 0.001) as well as p38 (25 μM, 0.366 ± 0.11; 50 μM, 0.403 ± 0.13; 100 μM, 0.362 ± 0.15; p < 0.001), JNK (25 μM, 0.443 ± 0.11; 50 μM, 0.514 ± 0.13; 100 μM, 0.372 ± 0.15; p < 0.001), and ERK (25 μM, 0.294 ± 0.01; 50 μM, 0.323 ± 0.01; 100 μM, 0.274 ± 0.01; p < 0.001) protein phosphorylation, which was accompanied by an upregulation of Nrf-2 (25 μM, 1.57 ± 0.01; 50 μM, 1.54 ± 0.01; 100 μM, 1.63 ± 0.05; p < 0.05) and HO-1­(25 μM, 2.12 ± 0,03; 50 μM, 2.24 ± 0.01; 100 μM, 1.92 ± 0.05; p < 0.01) expression in comparison with LPS–DMSO cells. Moreover, oleocanthal inhibited canonical and noncanonical inflammasome signaling pathways. Thus, oleocanthal might be a promising natural agent for future treatment of immune-inflammatory diseases.

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory autoimmune disease mainly characterized by aggressive hyperproliferation of synovial fibroblasts (SFs). It is accompained by a massive infiltration of inflammatory immune cells inducing progressive matrix degradation, destruction of cartilage and bone erosion through the production of inflammatory mediators. Oleuropein is the most prevalent phenolic component in olive leaves, seed, pulp and peel of unripe olives and is responsible for the characteristic bitter taste of unprocessed olives. This secoiridoid possesses well-documented pharmacological properties, including antioxidant and anti-inflammatory properties, and is available as a food supplement in Mediterranean countries. However, to date, anti-arthritic effects of oleuropein on SFs have not been yet elucidated. Thus, the aim of the present study was to investigate the potential effects of oleuropein, on IL-1β-induced production of inflammatory mediators and oxidative stress in the human synovial sarcoma cell line (SW982). In order to gain a better insight into mechanisms of action, signaling pathways were also explored. Cell viability was determined using the sulforhodamine B (SRB) assay. The expression of inflammatory cytokines IL-6, TNF-α, MMP-1 and MMP-3 was evaluated by ELISA. Moreover, changes in the protein expression of cyclooxygenase (COX)-2, microsomal prostaglandin E synthase-1 (mPGES-1) as well as mitogen-activated protein kinase (MAPKs), nuclear factor kappa B (NF-κB), and nuclear factor-erythroid 2-related and heme oxygenase-1 (HO-1) signalling pathways were analysed by western blot. Oleuropein exerted anti-inflammatory and anti-oxidant effects via down-regulation of MAPK and NF-κB signaling pathways and induction of Nrf2-linked HO-1 controlling the production of inflammatory mediators decreasing IL-6 and TNF-α cytokines, MMP-1 and MMP-3 levels and mPGES-1 and COX-2 overexpression. Thus, oleuropein might provide a basis for developing a new dietary strategy for the prevention and management of RA.

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The polyphenolic extract (PE) from extra virgin olive oil (EVOO) has been shown to possess important anti-inflammatory and joint protective properties in murine models of rheumatoid arthritis (RA). This study was designed to evaluate the effects of PE on IL-1β-activated human synovial fibroblasts SW982 cell line. PE from EVOO treatment inhibited IL-1β-induced matrix metalloproteases (P<0·001), TNF-α and IL-6 production (P<0·001). Similarly, IL-1β-induced cyclo-oxygenase-2 and microsomal PGE synthase-1 up-regulations were down-regulated by PE (P<0·001). Moreover, IL-1β-induced mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB activation were ameliorated by PE (P<0·001). These results suggest that PE from EVOO reduces the production of proinflammatory mediators in human synovial fibroblasts; particularly, these protective effects could be related to the inhibition of MAPK and NF-κB signalling pathways. Taken together, PE from EVOO probably could provide an attractive complement in management of diseases associated with over-activation of synovial fibroblasts, such as RA.