Background: Artemisia deserti Krasch belongs to Asteraceae family, and has many medicinal properties that used to treat a variety of diseases, including antihypertensive, invigorating blood circulation, antiallergy, antiviral, antitumor, and antioxidant. Methods: The objective of this study was the evaluation of cytotoxic and antioxidant activities as well as the chemical composition of A. deserti essential oil extracted by different extraction methods. These extraction methods included hydro-distillation (HD), salt-HD (Salt pretreatment followed by HD), maceration-HD (maceration pretreatment followed by HD), acid-HD (acid pretreatment followed by HD), ultrasound-HD (ultrasound pretreatment followed by HD), and enzyme-HD (enzyme pretreatment followed by HD). Results: The results revealed that the highest yield of essential oil was achieved by acid-HD (0.48% ± 0.11%). In all methods, the main compounds of essential oil were camphor (44.32%–66.80%), piperiton (14.11%–24.33%), and 1,8-cineole (4.85%–6.75%). The antioxidant property of essential oils was investigated using the DPPH method. Based on the results, the essential oils extracted by acid-HD and enzyme-HD methods had the highest property. The cytotoxic property of A. deserti essential oils was evaluated. The results demonstrated that the essential oil extracted by enzyme-HD indicated the highest cytotoxicity activity against human cervical carcinoma (HeLa) cells in both 24 and 48 h. Based on the gas chromatography-mass spectrometry results, 1,8-cineol, carvacrol, thymol, and myristicin were rich in the essential oil extracted by enzyme-HD, and the highest cytotoxicity activity of essential oil obtained by enzyme-HD method is probably related to these compounds. Conclusion: In addition, it was observed that enzyme-HD is an effective method in the extraction of essential oil with the highest antioxidant and cytotoxic activities.
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