Anticancer effect of nutritional supplements based on mixtures of food spices and aromatic herbs

Abstract

The use of aromatic and medicinal plants for therapeutic purposes by Algerian populations has been documented since antiquity. Although it was rich, this popular herbal medicine was not scientifically documented on the one hand, and on the other hand it required verified scientific foundations of the therapeutic use of different species. Among the diseases treated by aromatic and medicinal plants, cancer is considered a priority due to the significant increase of its incidence and the limitations of the different therapeutic approaches applied. It is in a context of scientific validation of knowledge linked to popular herbal medicine that this thesis project took place. Actually, the main objective of the present thesis was to investigate the biological effects and in particular the validation of the anti-cancer potential of selected medicinal plants and spices. The first stage of this study aimed to determine the plants and spices to be included in future investigations as well as contribute to documenting ethnobotanical data linked to the use of different aromatic and medicinal species. Therefore, a national multiregional study, the first of its kind in Algeria, was carried out. In this study, we documented and analyzed the ethnomedicinal uses of 167 species belonging to 70 families. Based on this study, several species of plants and spices were investigated for their chemical and biological profile, with a focus on their anticancer activities to select promising mixtures for further analyses. In total, 3 medicinal plants: Bryonia dioica, Aristolochia longa, and Ephedra alata, and 5 spices were explored chemically and biologically. In addition to the quantification of their phenolic, flavonoid and tannic contents, their phenolic profiles were determined by HPLC-DAD. The established profiles made it possible to quantify the presence of several phenolic compounds of great therapeutic importance such as rosmarinic acid, caffeic acid, trans-cinnamic acid, vanillin, kaempferol, chrysin, chlorogenic acid, quercetin, p-Coumaric acid, rutin, and apigenin. Differences were observed in the presence and quantity of these phenolic products between the different extracts and species. Subsequently, the antioxidant (DPPH, FRAP, TAC, H2O2), and anti-inflammatory (HRBC, albumin denaturation, and proteinase inhibition) activities were evaluated for each species. The results obtained showed that most of the extracts had significant antioxidant and anti-inflammatory activities, sometimes more marked than those of standard drugs. In order to verify their anticancer potential, the extracts of the different species studied were tested against three cancer lines (HT-29, PC-3, A549). The nontoxicity of the extracts was also evaluated against normal cells (CCD18-Co). Our results showed that the methanolic extract of the spice was able to reduce the growth of cancer cells HT-29, PC-3, and A-549 by 67.03%, 75.56%, and 62.96%, respectively with IC50s of 0.99±0.04, 1.66±0.05 and 1.94±0.06 log10 μg/mL. This extract was demonstrated to be non-cytotoxic against normal cells. By analyzing the results obtained from the anticancer activity, four mixtures of plants and spices were prepared and evaluated (antioxidant, anti-inflammatory and anticancer activity). These four mixtures were based on different formulations between four species: B. dioica, E. prunastri, T. imperati, and A. longa. The anticancer activity of the mixtures was evaluated in addition to their anti-angiogenic capacities. The three mixtures were characterized by remarkable biological activities. Among them, the mixture based on B. dioica, E. prunastri, T. imperati had demonstrated significant anticancer activity against HT-29, PC-3 and A-549 with IC50s of 1.48, 1.29 and 1.52 log10 μg/mL, respectively. In addition, it has been demonstrated its ability to inhibit the spread of cancer through its anti-angiogenic effect. For confirmation purpose, the phenolic components in this effective mixture were studied in silico. The investigation resulted in the identification of several molecules as potential drugs with prediction of their molecular mechanism. Keeping in view the promising synergistic anticancer potentials exhibited by plant-spice mixtures and especially those of the mixture made of B. dioica, E. prunastri and T. imperati, we suggest that these medicinal plants and spices could be a promising source of anticancer molecules.