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Jujube plant is a potential source of polyphenols with biological propreties. The purpose of this study was to investigate the application of ultrasound technique for extracting phenolic compounds (TPC) from seeds of Zizyphus lotus under optimization conditions based on response surface methodology. A maximum TPC, total flavonoids content (TFC), and total condensed tannins content (TTC) of 2383.10 ± 0.87 mg GAE/100g, 486.50 ± 0.38 mg QE/100g and 15,787.10 ± 0.10 mg CE/100g, respectively obtained under ethanol concentration 50.16%, sonication temperature 29.01 °C, sonication time 15.94 min and solvent-to-solid ratio 34.10:1 mL/g. The optimized extract was then evaluated for its antioxidant, antiacethylcholinesterase, antihypercholesterolemia, and antiproliferative activities. The results showed that ultrasound method is a green and safe method that can be used to effectively extract TPC from jujube seeds. The biological activity of Zizyphus extract exhibited a very good antioxidant against DPPH (EC50 = 0.39 µg/mL) and FRAP (1670.42 ± 6.5 mg/100 g). Additionally, it possesses acetylcholinesterase (AChE) inhibitory effect (IC50 = 0.93 ± 0.01 mg/mL) and HMGR inhibition (45.41%) using 100 µg/mL. The extract significantly inhibits cell proliferation on the MCF-7 and HepG2 tumor cell lines with an IC50 values of <0.05 and 3 ± 0.55 mg/mL, respectively. Therefore, the ultrasound method can be considered a method for obtaining a significant anticancer activity with respect to the lines and therefore makes it possible to recover a maximum of phenolic compounds in less time with an AChE and HMGR inhibitory activity. Thus, it can be suggested that Zls extract is a promising fruit for the development of supplementary dietary due to its potential behaviour as nutraceutical.

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