Loranthus europaeus with numerous therapeutic usages was chosen for further bioactivity assays and phytochemical analysis. The air‐dried grounded L. europaeus fruits were solvent extracted via Soxhlet apparatus. Afterwards, methanol extract was fractionated via different chromatographic methods and structures of the isolated pure compounds were elucidated with relative nuclear magnetic resonance spectra. Additionally, L. europaeus fruits essential oil was achieved through hydrodistillation and analyzed via gas chromatography‐mass spectrometry. Besides, the in vitro DPPH and nitric oxide antioxidant property of L. europaeus methanol extract alongside its phenolic and flavonoids content were evaluated. MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay was carried out in A549 cancer cells and normal HUVECs cells for evaluating cytotoxicity of the plant extract and essential oil. Structure of the isolated major compounds of the extract were determined as two flavonoids. Analysis of the L. europaeus essential oil showed that it principally contained germacrene D (32.8%), β‐caryophyllene (19.2%) and alloaromadendrene (11.0%). In the MTT assay, 300 µg/mL of methanol extract caused ≈60% A549 cells death after 48 h with IC50 of 226 µg/mL. Likewise, the IC50 of the essential oil against A‐549 cell line for the 100 µg/mL L. europaeus fruits in 48 h was equal to 69 µg/mL. Overall, the present study is the first report on the phytochemical analysis of L. europaeus revealing occurrence of rhamnocitrin‐3‐O‐rhamnoside and rhamnetin‐3‐O‐rhamnoside in the plant extract alongside its high content of sesquiterpenoids in its essential oil. The observed antiproliferative activity of L. europaeus methanol extract against A549 cancer cells rather than healthy cells indicated its anti‐tumor properties which might be related to the high values of phenolic and flavonoids content in the methanol extract of the plant associated with its superior in vitro antioxidant activities.
