Toxicity Effects of Ganoderma lucidum ethanol extract on Cognition and Anxiogenic-like behavior is dose-dependent in Swiss mice
Keywords:
Ganoderma lucidum, Cognition, Anxiogenic, Neurotoxic, Cholinergic, Oxidative stressAbstract
Ganoderma lucidum as one of the folk medicinal mushrooms has been used for the prevention and treatment of diverse disorders including neurasthenia, dizziness, anorexia, hypertension, deficiency fatigue, and arthritis, but its CNS-related safety is scanty and undefined. This research was designed to evaluate the toxicity effects of Ganoderma lucidum ethanol extract (EEGL) on cognitive and anxiogenic-like behaviours in Swiss mice. Forty Swiss mice (n = 5/group) of both sexes were treated orally with distilled water (10 mL/kg; vehicle), and graded doses of EEGL (100, 200, and 400 mg/kg, respectively) for 30 days, during which neurobehavioral data from Morris water maze, light/dark box, and open field test were obtained. Thereafter, neurochemical and histological assessments were evaluated. The EEGL-treated groups showed a significant reduction in spatial cognitive performance in males without remarkable difference in females except at high dose (400 mg/kg). A high dose of EEGL induced anxiety-like behaviours by significantly increasing time spent in the dark compartment and decreasing the number of transitions in the light/dark box, as well as increasing time spent in the outer zone of the open field apparatus. Furthermore, EEGL at higher doses (≥ 200 mg/kg) disrupted neurochemicals significantly by decreasing glutathione, superoxide dismutase and catalase activities while remarkably increasing malondialdehyde, nitric oxide, acetylcholinesterase, tumor necrosis factor-alpha, and interleukin-6 levels. Consequently, exposure to a high dose of EEGL resulted in mild hippocampal alterations in males, while the prefrontal cortex appeared normal. Taken together, EEGL shows potential neurotoxic effects at doses greater than 100 mg/kg for 30 days, while lesser doses might be beneficial.