Neuroprotective properties of Linzia gerberiformis aqueous leaves extract against aluminium chloride (AlCl3) -induced cognitive impairment: Involvement of cholinergic, GABAergic, and antioxidant mechanisms

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by oxidative imbalance, leading to memory deficits and cognitive impairments. Aluminium chloride (AlCl 3 ), a neurotoxin found in certain foods and medications, disrupts neurotransmitter systems, thereby exacerbating cognitive decline. Current drug development strategies aim to counter these effects through cholinesterase inhibition, activation of GABAergic transmission, the use of antioxidants, and the promotion of neuroprotection. This work was conducted to assess the neuroprotective properties of the aqueous extract of Linzia gerberiformis ( L. gerberiformis ) leaves against AlCl 3 induced cognitive impairment in mice. AlCl 3 (70 mg/kg) was administered orally in mice to induced memory loss a core feature of Alzheimer Disease. Mice were pretreated with aqueous extract of L. gerberiformis leaves (75, 150 and 300 mg/kg) for six weeks, and memory integrity was assessed using the object location test (OLT) and the T-Maze test. One hour after completion of the T-Maze, the mice were sacrificed, the hippocampus and prefrontal cortex were then collected to assess the cholinergic (acetylcholinesterase (AChE) and acetylcholine (ACh)), GABAergic systems and oxidative stress (nitric oxide (NO), malondialdehyde (MDA) SOD, Catalase (CAT), reduced glutathione (GSH)). The aqueous extract of L. gerberiformis leaves demonstrated significant effects (P < 0.01 and P < 0.05) at doses of 75 and 150 mg/kg in improving short-term learning memory, as well as a significant enhancement (P < 0.05) of long-term spatial memory on day 3 at the dose of 75 mg/kg. AlCl 3 (70 mg/kg) induced increase in AChE (P < 0.05; P < 0.01), NO (P < 0.05; P < 0.001), and MDA (P < 0.05; P < 0.01), while decreasing ACh (P < 0.01), GABA (P < 0.05; P < 0.01), SOD (P < 0.01; P < 0.001), CAT (P < 0.05), and GSH (P < 0.01) in the hippocampus and prefrontal cortex. Pretreatment with aqueous extract of L. gerberiformis leaves significantly restored these parameters (P < 0.01; P < 0.001) for Ach at the doses 75 and 150 mg/kg and GABA (P < 0.05) at all doses. Significant improvement was also observed for SOD (P < 0.05 and P < 0.01), GSH, and MDA (P < 0.05 and P < 0.01), as well as for NO (P < 0.05 and P < 0.01) in both the hippocampus and prefrontal cortex. The present study established that the aqueous extract of L. gerberiformis leaves ameliorated AlCl 3 -induced neurotoxicity by modulating the activation of the cholinergic, GABAergic and antioxidant pathways.