Neurobehavioral outcomes of Achillea fragrantissima ethanolic extract in male rats: modulation of GABAergic signaling, monoaminergic expression, neuroplasticity markers (BDNF, ARC), and oxidative stress

This research aimed to examine the impact of the ethanolic extract of Achillea fragrantissima aerial parts (ACF) on the rat CNS. Forty mature Sprague–Dawley male rats were assigned to four groupings (n = 10): 1st C: (control), 2nd DIZ: (diazepam), 3rd ACF-H: (800 mg/kg extract high-dose extract), and 4th ACF-L: (400 mg/kg low-dose extract) gavaged daily for 14 days. The HPLC-identified components are naringenin, ferulic acid, catechin, chlorogenic acid, diadzein, syringic acid, rutin, hesperetin, kaempferol, caffeic acid, vanillin, and quercetin. The effect of ACF extract on rat CNS was measured using the Open field, Hole-cross, Rotarod, Negative geotaxis, and Wrist-grip tests. ACF extract administration substantially (P < 0.05) reduced locomotor and exploratory behaviors in the open-field and hole-cross tests. In the negative geotaxis test, rats administered ACF extract exhibited a substantial delay (P < 0.05) in the turning 180° to a head-up position. In the rotarod and wrist-grip tests, the fall-off time and the latency to fall were considerably reduced (P < 0.05). Administration of ACF extract significantly (P < 0.05) elevated the brain GABA levels, while the increase in dopamine concentrations was observed but should be interpreted cautiously because these findings require confirmation using more specific analytical methods. Additionally, the extract significantly increased the total antioxidant capacity (TAC), but reduced lipid peroxidation (MDA), 8-hydroxy-2-deoxyguanosine (8OH2dG), and protein carbonyl (PCO) levels. ACF oral administration significantly (P < 0.05) upregulated brain GABAA receptor-linked protein (GABARAP), activity-regulated cytoskeleton-linked protein (ARC), and brain-derived neurotrophic factor (BDNF), meanwhile, significantly downregulated the monoamine oxidase A (MAOA) brain levels. For the first time, the outcomes of the ongoing trial demonstrated the in vivo promising effects of A. fragrantissima aerial parts ethanolic extract on neurobehavioral and antioxidant status in an animal model. Graphical abstract