Abstract
BackgroundPsychosis is a complex mental illness divided by positive symptoms, negative symptoms, and cognitive decline. Clinically available medicines are associated with some serious side effects which limit their use. Treatment with flavonoids has been associated with delayed onset and development, decreased risk, or increased improvement of various neuropsychiatric disorders including psychosis with negligible side effects. Therefore, the present study was aimed to investigate the protective effects of hesperidin (flavonoid) alone or its combination with coenzyme Q10 against ketamine-induced psychotic symptoms in mice.ResultsKetamine (50 mg/kg, i.p.) was given for 21 days to induce psychosis in Laca mice of either sex. Locomotor activity and stereotypic behaviors, immobility duration (forced swim test), and increased transfer latency (elevated plus maze) were performed to test the effect of hesperidin (50 mg/kg, 100 mg/kg, 200 mg/kg, p.o.) and coenzyme Q10 (20 mg/kg, 40 mg/kg, p.o.) and combination of hesperidin + coenzyme Q10 followed by biochemical and mitochondrial complexes assays. For 21 days, ketamine (50 mg/kg, i.p.) administration significantly produced increased locomotor activity and stereotypic behaviors (positive symptoms), increased immobility duration (negative symptoms) and cognitive deficits (increases transfer latency) weakens oxidative defense and mitochondrial function. Further, 21 days’ administration of hesperidin and coenzyme Q10 significantly reversed the ketamine-induced psychotic behavioral changes and biochemical alterations and mitochondrial dysfunction in the discrete areas (prefrontal cortex and hippocampus) of mice brains. The potential effect of these drugs was comparable to olanzapine treatment. Moreover, the combination of hesperidin with coenzyme Q10 and or a combination of hesperidin + coenzyme Q10 + olanzapine treatment did not produce a significant effect compared to their per se effect in ketamine-treated animals.ConclusionsThe study revealed that hesperidin alone or in combination with coenzyme Q10 could reduce psychotic symptoms and improve mitochondrial functions and antioxidant systems in mice, suggesting neuroprotective effects against psychosis.
Highlights
Psychosis is a complex mental illness divided by positive symptoms, negative symptoms, and cognitive decline
Behavioral assessments Effect of hesperidin and coenzyme Q10 on locomotor activity using actophotometer Ketamine (50 mg/kg, i.p.) treatment significantly (p < 0.05) caused hyperlocomotion on days 7 and 14 and hypolocomotion on day 21 compared to the naïve group
Effect of hesperidin and coenzyme Q10 on immobility duration using forced swim test Ketamine (50 mg/kg) treatment significantly (p < 0.05) increased the immobility duration in the forced swim test on day 21 compared to the naïve group
Summary
Psychosis is a complex mental illness divided by positive symptoms, negative symptoms, and cognitive decline. Treatment with flavonoids has been associated with delayed onset and development, decreased risk, or increased improvement of various neuropsychiatric disorders including psychosis with negligible side effects. The present study was aimed to investigate the protective effects of hesperidin (flavonoid) alone or its combination with coenzyme Q10 against ketamine-induced psychotic symptoms in mice. Psychosis is a psychological multifactorial disorder categorized into positive symptoms (delusions, hallucinations), negative symptoms (apathy, suicidal thoughts, social detachment), and cognitive decline [1]. Oxidative stress has been associated with the worsening of neuropsychiatric disorders like psychosis. Oxidative stress is reported to cause mitochondrial dysfunction which further leads to produce psychotic symptoms especially negative and cognitive symptoms. Ketamine is reported to produce mitochondrial dysfunction and oxidative stress that further lead to cause psychosis in mice [2]. There is an emerging need to investigate such a therapeutic agent by exploring new pathways that can overcome these side effects against psychotic symptoms [1]
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