en Other Other پژوهشي orginal article <span style="font-size:16px;"><span style="line-height:1;"><span style="font-family:Times New Roman;"><strong>Background:</strong> <em>Guiera senegalensis</em> is widely used in African ethnomedicine for treating neurological and inflammatory disorders, yet its safety and neuropharmacological profile remain incompletely defined.<br> <strong>Objective:</strong> This study evaluated the phytochemical composition, neurobehavioral effects, and toxicity profile of the methanolic leaf extract of <em>G. senegalensis</em> in Wistar rats.<br> <strong>Methods:</strong> Phytochemical screening was conducted using standard protocols. Acute toxicity was assessed per the Organisation for Economic Co-operation and Development (OECD) 423 guidelines at 2000 mg/kg, while subacute toxicity involved 28-day oral administration (125&ndash;500 mg/kg) with hematological, biochemical, and histopathological evaluations. Neurobehavioral effects were investigated using ketamine-induced psychosis models (open field and Y-maze tests).<br> <strong>Results:</strong> Phytochemical analysis revealed tannins, saponins, flavonoids, glycosides, and steroids. Acute toxicity testing showed no mortality up to 2000 mg/kg. In the open field test, methanolic leaf extract of <em>G. senegalensis</em> modestly attenuated ketamine-induced hyperlocomotion, with 800 mg/kg exerting the strongest antipsychotic-like effect. In the Y-maze, intermediate doses (200&ndash;400 mg/kg) preserved working memory, while 800 mg/kg caused severe cognitive impairment. Subacute administration induced variable hematological and biochemical alterations, including elevated platelet indices, increased Aspartate Aminotransferase, and hyperbilirubinemia at 250&ndash;500 mg/kg. Histopathology revealed progressive hepatocellular degeneration and renal tubular necrosis.<br> <strong>Conclusion:</strong> Methanolic leaf extract of <em>G. senegalensis</em> exhibits antipsychotic-like and cognition-modulating properties, but produces progressive hepatotoxicity and nephrotoxicity upon subacute exposure. The most consistent evidence of toxicity was derived from histopathology, whereas hematological and biochemical markers showed non-monotonic responses. These findings suggest a narrow therapeutic margin for the methanolic leaf extract of <em>G. senegalensis</em> and highlight the need for quantitative phytochemical profiling, mechanistic studies, and dose&ndash;response bridging to define its pharmacological potential and safety.</span></span></span> Antipsychotic, Guiera senegalensis, Hepatotoxicity, Nephrotoxicity, Neurobehavior, Phytochemistry 334 344 http://ijrabms.umsu.ac.ir/browse.php?a_code=A-10-570-2&slc_lang=en&sid=1 Albashir Tahir albashirtahir@sazu.edu.ng 10031947532846005561 10031947532846005561 Yes Department of Pharmacology, Faculty of Basic Medical Sciences, Sa’adu Zungur University, Bauchi State, Nigeria Ibrahim Khaleel Muazu ibrahimkhaleel@fedpodam.edu.ng 10031947532846005562 0009-0004-8598-4543 No Department of Pharmaceutical Technology, Federal Polytechnic Damaturu, Yobe State, Nigeria Nura Bello bnura@abu.edu.ng 10031947532846005563 10031947532846005563 No Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria Mubarak Idris mubarakidris@sazu.edu.ng 10031947532846005564 10031947532846005564 No Department of Biochemistry, Faculty of Sciences, Sa’adu Zungur University, Bauchi State, Nigeria Adamu Abdullahi adamu@sazu.edu.ng 10031947532846005565 0009-0003-6243-2319 No Department of Biochemistry, Faculty of Sciences, Sa’adu Zungur University, Bauchi State, Nigeria Yasir Idris Saleh iysaleh@sazu.edu.ng 10031947532846005566 0009-0004-0609-2302 No Department of Biochemistry, Faculty of Sciences, Sa’adu Zungur University, Bauchi State, Nigeria Abbas Nasidi abbasnasidi@sazu.edu.ng 10031947532846005567 10031947532846005567 No Department of Anatomy, Faculty of Basic Medical Sciences, Sa’adu Zungur University, Bauchi State, Nigeria