Antipsychotic effects of aqueous lyophilisate of Ficus mucuso on ketamine-induced schizophrenia

Abstract

Nutraceuticals and medicinal plants have been studied for the treatment of schizophrenia. Ficus mucuso is a medicinal plant used in Cameroon to treat epilepsy, jaundice, and schizoaffective disorders. Schizophrenia is a heterogeneous and ubiquitous neuropsychiatric disorder associated with neurochemical and oxidative disturbances characterized by the appearance of a triad of psychotic symptoms. This study investigated the antipsychotic effect of the aqueous lyophilisate of F. mucuso on behavioral disturbances, oxidative and neurochemical imbalances, and ketamine-induced neurodegeneration in white mice. In the curative approach of the study, mice received a single daily dose of ketamine (20 mg/kg, i.p.) for 14 days and were then treated 30 min later with the aqueous lyophilisate of F. mucuso (25, 50 and 100 mg/kg, p.o.) or risperidone from days 8 to 14. Behavioral deficits were measured using stereotyped climbing, open field, forced swimming, and Y-maze tests, followed by sacrifice. Neurochemical and oxidative imbalances were assessed by spectrophotometry in the hippocampus, prefrontal cortex, and striatum. Histological sections of brain structures were analyzed and cell counts were performed. F. mucuso improved behavioral abnormalities and memory deficits in ketamine-treated mice. In addition, it reversed ketamine-induced oxidative stress by significantly increasing ( p < 0.001) glutathione, catalase, and superoxide dismutase activity and significantly decreasing ( p < 0.001) malondialdehyde and nitrite oxide levels in the hippocampus, prefrontal cortex and striatum. Similarly, it significantly reduced ( p < 0.001) the concentration of dopamine, serotonin, acetylcholinesterase activity, and GABA-T, and significantly increased ( p < 0.001) the concentration of GABA and glutamate in the hippocampus, prefrontal cortex, and striatum. Histology showed that F. mucuso protected cellular structures by reducing neurodegeneration and increasing the number of nucleated cells. In conclusion, F. mucuso improved ketamine-induced neurobehavioral deficits and neurodegeneration by modulating neurotransmitters, increasing the antioxidant system, and restoring the integrity of cellular structures.