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Achyranthes aspera L. (Prickly Chaff flower) is an imperative Asian herb that has been known for numerous healing powers. The aim of this research is to investigate the pharmacological i.e., antidepressant and anxiolytic properties of the methanol extract of aerial part of A. aspera (MEAA) by in vivo and in silico approaches. Additionally, thrombolytic potential of the crude extract has also been explored. The antidepressant and anxiolytic investigations were performed by force swimming test (FST), tail suspension test (TST), and hole board test (HBT) in mice, whereas clot lysis activity test was conducted using thrombolytic experimental method. Furthermore, in silico studies were appraised with Discovery studio, PyRx, UCSF Chimera whereas, PASS prediction, and ADME/T was implemented using online tools. Treatment with MEAA revealed significant (p < 0.05) reduction of immobility time in FST and TST …