Oleuropein-Rich Leaf Extract as a Broad Inhibitor of Tumour and Macrophage iNOS in an Apc Mutant Rat Model

Abstract

Oleuropein, the major compound found in olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, anti-diabetic and anti-cancer effects. The purpose of this study was to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours arising in Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, representing a critical and abundant population in most solid tumour microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We this confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1β, IL-6 and TGF-β. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

Oleuropein-Rich Olive Leaf Extract Attenuates Neuroinflammation in the Alzheimer’s Disease Mouse Model

“…However, it is worth mentioning that while OLE-reduced inflammation could result from its direct suppression of the NF-κB pathway, which subsequently inhibits the activation of NLRP3 inflammasomes and RAGE/HMGB1 pathways, the effect could also be indirectly mediated by the reduction of Aβ brain levels. Additional studies would be necessary for confirmation; however, several in vitro studies demonstrated that oleuropein has a direct modulatory effect on inflammation, ,− suggesting that oleuropein reduces neuroinflammation via both suppressing the NF-κB pathway and Aβ reduction.…”

Therapeutic Properties and Use of Extra Virgin Olive Oil in Clinical Nutrition: A Narrative Review and Literature Update

“…An extensive review of the effects of EVOO and its minor components in preclinical models of colon cancer is also available [ 331 ]. Oleuropein-rich EVOO stimulated in vivo apoptosis of colon cancer cells and peritoneal macrophages in an animal model [ 332 ], and a much more potent nanoencapsulated microemulsion of oleuropein was recently developed and tested in an animal model [ 333 ]. While the addition of oleic acid induced DNA synthesis and growth of the human colorectal adenocarcinoma cell line Caco-2, the subsequent addition of EVOO’s minor components prevented this effect, even inducing apoptosis in the case of hydroxytyrosol and maslinic acid [ 330 ].…”

Extra Virgin Olive Oil and Cardiovascular Protection in Chronic Kidney Disease

“…Viability of the cells was determined by trypan blue exclusion test. Cultures were periodically monitored for Mycoplasma contamination using Chen’s fluorochrome test, as described in a previous study of ours [ 33 ].…”

“…Results were normalized to protein concentration. For RAW264.7 cells, nitrite production was expressed with reference to lipopolysaccharide (LPS; Sigma) as 100% [ 33 ].…”