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Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized theS. fruticosum seed’s fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro,and in silico studies. The SF was fractionated with different solvents, and the ethyl acetate fraction of SF (EaF-SF) was further studied. Mice treated with EaF-SF (200 and 400 mg/kg) manifested anxiolysis evidenced by higher exploration in elevated plus maze and hole board tests. Similarly, a dose-dependent drop of immobility time in a forced swimming test ensured significant anti-depressant activity. Moreover, higher dose treatment exposed reduced exploratory behaviour resembling decreased movement and prolonged sleeping latency with a quick onset of sleepduring the open field and thiopental-induced sleeping tests, respectively. Inparallel, EaF-SF significantly (p < 0.001) and dose-dependently suppressed aceticacid and formalin-induced pain in mice. Also, a noteworthy anti-inflammatoryactivity and a substantial (p < 0.01) clot lysis activity (thrombolytic) was observed. Gas chromatography-mass spectrometry (GC–MS) analysis resulted in 49 bioactive compounds. Among them, 12 bioactive compounds with Lipinski’s rule and safety confirmation showed strong bindingaffinity (molecular docking) against the receptors of each model used. Toconclude, the S. fruticosum seed isa prospective source of health-promotingeffects that can be an excellent candidate for preventing degenerative diseases.

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