The Action Mechanisms, Anti-Cancer and Antibiotic-Modulation Potential of Vaccinium myrtillus L. Extract.

BACKGROUND: Herbal medicinal products containing Vaccinium myrtillus L. (bilberry) fruits and fruit extracts are widely available in the market. Although bilberry leaves and stems are considered as bio-waste, they contain much higher levels of phenolic compounds than fruits. The study aimed to investigate the antimicrobial and anticancer potential of aerial part extracts from Vaccinium myrtillus L. (V. myrtillus, VM) plants harvested at high altitudes in Armenian landscape and characterize the bioactive phytochemicals. MATERIAL AND METHODS: For evaluation of antioxidant properties, chemical-based tests (total phenolic and flavonoid content, and antiradical activity in 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) tests) and cellular antioxidant activity (CAA) assay were applied. Genotoxicity and anticancer properties of the extract alone and in combination with fluorouracil were explored in human cancer and normal cell lines. Antibacterial properties of V. myrtillus extract alone and in combination with antibiotics, as well as their effect on proton-flux rate through cell membrane were explored on bacterial strains. The characterization of active phytochemicals was done using Liquid Chromatography-Quadrupole-Orbitrap High-Resolution Mass Spectrometry (LC-Q-Orbitrap HRMS). RESULTS: The V. myrtillus aerial part extract demonstrated promising antioxidant properties in all tests. The selective cytotoxic activity was documented against various cancer cell lines (human colon adenocarcinoma (HT29), human breast cancer (MCF-7) and human cervical carcinoma (HeLa)), while it did not inhibit the growth of tested human normal primary renal mixed epithelial cells (HREC) even at 10-fold higher concentrations. The extract did not have genotoxic properties in comet assay making it a potential source for the development of anticancer preparations. The investigated extract did not directly inhibit the growth of Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium) strains at up to 1 mg/mL concentration. However, V. myrtillus extract enhanced the kanamycin intake and increased its efficiency against E. coli strain. The phytochemical characterization of the extract showed the presence of different groups of phenolics. CONCLUSIONS: Based on obtained data, we suggest the aerial parts of the V. myrtillus plant as an alternative source of bioactive natural products for food supplements, nutraceuticals, functional foods and medicine.

Essential Oil and Ethanol Extract of Oregano (Origanum vulgare L.) from Armenian Flora as a Natural Source of Terpenes, Flavonoids and other Phytochemicals with Antiradical, Antioxidant, Metal Chelating, Tyrosinase Inhibitory and Antibacterial Activity.

BACKGROUND: Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in vitro. METHODS: EO of plant aerial parts was extracted by the hydro-distillation method, and the composition was analyzed by gas-chromatography (GC). EE was prepared using ethanol as a solvent. Antioxidant, antibacterial and other biological activity of EO and EE was determined using appropriate methods. RESULTS: The terpenes were found to be the greatest part of oregano EO (ß-caryophyllene epoxide - 13.3 %; ß- caryophyllene -8.2 %; ο-cymene - 5.2 %). The flavonoid content of EE was 3.9±0.7 mg g-1 catechin equivalents. Antiradical activities of EO and EE expressed with half-maximum inhibitory concentrations were 1057 µg mL-1 and 19.97 µg mL-1. The antioxidant index in the case of using extract (1000 µg mL-1) was 77.3±1.5 %. The metal chelating activity of EE was 74.5±0.2 %. The tyrosinase inhibitory activities of EO, EE and arbutin were 26.5±0.3 %, 6.5±0.2 % and 50±0.1 %, respectively. Both EO and EE of oregano were able to suppress the growth of testmicroorganisms including clinical pathogen isolates, but have moderate antimicrobial activity. EO antibacterial activity against ampicillin-resistant Escherichia coli was similar to the activity against non-resistant strain. EE was not active against ampicillin-resistant E. coli in contrast to non-resistant one. CONCLUSION: The results indicate high antioxidant and moderate antibacterial as well as high antiradical, metal chelating, tyrosinase inhibitory activity of oregano EO and EE, which can be used as a natural source of terpenes, flavonoids and other phytochemicals in medicine, pharmaceutics, cosmetics and food industry. EO has antibacterial activity also against ampicillin-resistant E. coli.