Background: Arbutus andrachne L. is a perennial evergreen shrub widely distributed throughout the Mediterranean region. This plant holds great scientific significance owing to its nutritional, pharmacological, and chemical characteristics, making it a popular choice as a medicinal plant. It is well known for its diverse applications in science and medicine. Objectives: The primary purposes of this study were to explore the antioxidant and antiproliferative properties of A. andrachne and to identify the phytochemicals in A. andrachne essential oil. Methods: The fruits of A. andrachne L. were collected and taxonomically identified. Aqueous, ethanolic, and methanolic extracts were then prepared. The fruits of A. andrachne were subjected to advanced hydrodistillation to extract essential oils, which were carefully analyzed using gas chromatography-mass spectrometry (GC-MS) to identify their phytochemical components. A ferric-reducing antioxidant power assay was used to test the extracts' antioxidant activity. The colorimetric assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) was used to test the extracts' antiproliferative activity against five specific cell lines: T47D and MCF-7 (breast cancer), Caco-2 and HCT-116 (colorectal cancer), and MRC-5 (a standard fibroblast cell line used as a control). Results: The main findings indicated that the essential oil of the fruits comprises 35 different components. The main ingredient in A. andrachne fruits is pentadecanoic acid, 14-methyl-, methyl ester (19.87%). The methanolic extract exhibited the highest antioxidant activity (18.27 µmol/L Fe2+ equivalents). Furthermore, all tested extracts exerted weak antiproliferative activity against the tested cancerous cell lines and had no significant effect on normal cell lines. At 200 µg/mL, the aqueous, methanolic, and ethanolic extracts showed high viability of the treated cells across all tested cell lines (ranging from 99.30 - 100.00%). Conclusions: The A. andrachne crude extracts, with their non-cytotoxic activity on both cancerous and normal cells, present a promising natural source of antioxidants. This potential opens up various applications in the food and pharmaceutical industries, highlighting the relevance and impact of these findings.
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