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<title>Abstract</title> This current study aimed to examine the depressive outcome of <italic>Artemisia monosperma Delile</italic> ethanolic extract (ARM-EE) on the central nervous system (CNS) of male rats. Screening phytochemicals was done using GC˗MS and HPLC analysis. The study included four equal groups (n = 10): 1st Control, 2nd Diazepam (DIZ 1 mg/kg B.wt.), 3rd ARM high group (ARM-H 800 mg/kg B.wt.), and 4th ARM low group (ARM-L 400 mg/kg B.wt). Dosing was orally and daily for 21 days. The acute oral LD <sub>50</sub> was valued to be more than 2 g/kg. HPLC analysis revealed the presence of vanillin, syringic acid, naringenin, coffeic acid, rutin, gallic acid, and querectin. Administration of ARM-EE extract significantly <italic>(p < 0.001)</italic> decreased the hole crosses and fall-off time in the rotarod test. In the open field test, ARM-EE significantly <italic>(p < 0.001)</italic> decreased locomotor and exploratory behaviors. ARM-EE administration significantly <italic>(p < 0.05)</italic> increased the brain γ-aminobutyric acid (GABA), dopamine (DA), and serotonin (5˗HT) levels. ARM-EE administration significantly <italic>(p < 0.05)</italic> up-regulated the brain mRNA expression levels of <italic>GABA</italic> type a receptor-associated protein ( <italic>Gabarap</italic> ) and brain-derived neurotrophic factor ( <italic>BDNF</italic> ), meanwhile, expression levels of monoamine oxidase A ( <italic>Maoa</italic> ) was significantly <italic>(p < 0.05)</italic> downregulated. The results of the ongoing research suggest for the first time that the <italic>A. monosperma</italic> ethanolic extract owns CNS depressant and antioxidative outcomes in a murine model. The CNS-depressive properties of the ARM-EE could be attributable to its phytochemical components. Further toxicological studies are required for the semi-purified phytochemical components of the ARM plant.
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DOI: 10.21203/rs.3.rs-5338696/v1
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