Antitumoral and Immunomodulatory Effect of Mahonia aquifolium Extracts

Abstract

The prodrug potential of Mahonia aquifolium, a plant used for centuries in traditional medicine, recently gained visibility in the literature, and the activity of several active compounds isolated from its extracts was studied on biologic systems in vitro and in vivo. Whereas the antioxidative and antitumor activities of M. aquifolium-derived compounds were studied at some extent, there are very few data about their outcome on the immune system and tumor cells. To elucidate the M. aquifolium potential immunomodulatory and antiproliferative effects, the bark, leaf, flower, green fruit, and ripe fruit extracts from the plant were tested on peripheral blood mononuclear cells and tumor cells. The extracts exert fine-tuned control on the immune response, by modulating the CD25 lymphocyte activation pathway, the interleukin-10 signaling, and the tumor necrosis-alpha secretion in four distinct human peripheral blood mononuclear cell (PBMC) subpopulations. M. aquifolium extracts exhibit a moderate cytotoxicity and changes in the signaling pathways linked to cell adhesion, proliferation, migration, and apoptosis of the tumor cells. These results open perspectives to further investigation of the M. aquifolium extract prodrug potential.

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“…A healthy male volunteer, aged 44, donated the peripheral blood following provision of written informed consent. The lymphocytes were isolated on Histopaque 1.077 cell separation solution (from Sigma Aldrich St. Louis, MO, USA), following protocol described elsewhere [46], aliquoted, and kept in a liquid nitrogen tank (Cryosystem 2000, MVE Bio-Medical Division, Burnsville, USA)…”

“…From the whole PBMC population, the CD4+, CD8+, CD14+, CD19+, CD45RA+, and CD69+ subsets were isolated using magnetic separation methods [46] (MACS system, MS magnetic columns, and magnetic beads from MiltenyiBiotec, BergischGladbach, Germany). The whole PBMC population was placed on 24-well plates with a cell suspension density of 10 5 cells/mL of cell culture media (RPMI-1640 supplemented with 10% fetal calf serum, 1% nonessential amino acid solution, 1% sodium pyruvate, and 1% glutamine solution; all media and supplements were obtained from Sigma Aldrich).…”

“…The cell viability of lymphocytes was assessed as described earlier [46]. In the second assay plate loaded with samples, the wells were treated with 20 µL of [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)] 2-(4-sulfophenyl)-2H-tetrazolium salt and phenazinemethosulfate mixture (MTS:PMS in a volume proportion of 20:1), with the reagents comprising the CellTiter 96 Aqueous Non-Radioactive Cell Proliferation Assay kit from Promega Corporation, Madison, WI, USA.…”

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“…M. aquifolia has various pharmacological activities as anti-oxidant activity and anti-infl ammatory activity [156][157][158], Anti-bacterial [155,159,160], Anti-fungal activity [161], Antitumoral and Immunomodulatory activity [162].…”

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“…100 Oregon grape [Mahonia aquifolium, Berberidaceae] M. aquifolium is native to United states of America, and known worldwide to be an ornamental plant. 101 Various pharmacological activities were reported for this plant as anti-bacterial, [101][102][103] antifungal, 104 anti-inflammatory, [105][106][107] antitumoral and immunomodulatory 108 activities. The anti-bacterial activity of M. aquifolium is based on two alkaloids, berberine chloride and oxyacanthine sulphate extracted from the stem bark.…”