Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 28 July 2021 / Approved: 30 July 2021 / Online: 30 July 2021 (12:32:16 CEST)
Version 2 : Received: 30 July 2021 / Approved: 2 August 2021 / Online: 2 August 2021 (12:04:58 CEST)

A peer-reviewed article of this Preprint also exists.

Ruzzolini, J.; Chioccioli, S.; Monaco, N.; Peppicelli, S.; Andreucci, E.; Urciuoli, S.; Romani, A.; Luceri, C.; Tortora, K.; Calorini, L.; Caderni, G.; Nediani, C.; Bianchini, F. Oleuropein-Rich Leaf Extract as a Broad Inhibitor of Tumour and Macrophage iNOS in an Apc Mutant Rat Model. Antioxidants 2021, 10, 1577. Ruzzolini, J.; Chioccioli, S.; Monaco, N.; Peppicelli, S.; Andreucci, E.; Urciuoli, S.; Romani, A.; Luceri, C.; Tortora, K.; Calorini, L.; Caderni, G.; Nediani, C.; Bianchini, F. Oleuropein-Rich Leaf Extract as a Broad Inhibitor of Tumour and Macrophage iNOS in an Apc Mutant Rat Model. Antioxidants 2021, 10, 1577.

Abstract

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an 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, which represents a critical and abundant population in most solid tumours 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 confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. 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.

Keywords

Oleuropein; colon cancer; activated macrophages; chronic inflammation; inducible nitric oxide synthetase (iNOS); cyclooxygenase-2 (COX-2); nitric oxide (NO)

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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