Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients

Abstract

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 μg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC.

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

“…As discussed previously, our results indicate an important role for MSC in reducing the pathogenic Th17 response in experimental colitis, in agreement with Godoi et al [16], who observed reduced levels of IL-17 after bone marrow transplantation for the treatment of experimental intestinal inflammation. Th17 cells and the cytokine IL-17 have been found at elevated levels in intestinal tissue and serum from patients with IBD, confirming the finding that this pattern of immune response contributes to the development of the disease [64]. Interestingly, we also show that MSC infusion reduced the frequency of IL-17/IFN-γ double-producing cells at spleen, which was followed by a decreased accumulation of neutrophils in the colon of treated mice.…”

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

“…OLE inhibited canonical and noncanonical inflammasome signaling pathways [50] J774 LPS-stimulated macrophages 50 µM OLE inhibited LPS-induced NO production without affecting cell viability [117] OL reduced the expression of COX-2 and IL-17 in samples treated with OL. In addition, OL ameliorated inflammatory tissular damage [207]…”

Oleuropein, a Bioactive Compound from Olea europaea L., as a Potential Preventive and Therapeutic Agent in Non-Communicable Diseases

“…Recently, a study by Larussa T. et al [68] demonstrated that the administration of OleA on colonic biopsies taken from ulcerative colitis patients led to a decrease of COX-2 and IL-17 levels, considerably reducing the inflammation of the colonic tissue. This evidence encourages the use of oleuropein as an inflammation-modulator.…”