Neuroprotective effect of hesperidin and its combination with coenzyme Q10 on an animal model of ketamine-induced psychosis: behavioral changes, mitochondrial dysfunctions, and oxidative stress
Naresh Kumar, M. Yadav, Ashok Kumar, Monika Kadian, Sunil Kumar
Future Journal of Pharmaceutical Sciences January 15, 2022 DOI: 10.1186/s43094-022-00402-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Laca mice of either sex with ketamine-induced psychosis-like symptoms |
| Interventions | Hesperidin Coenzyme Q10 Olanzapine Ketamine |
| Dose | Ketamine 50 mg/kg i.p.; hesperidin 50 mg/kg, 100 mg/kg, 200 mg/kg p.o.; coenzyme Q10 20 mg/kg, 40 mg/kg p.o. |
| Duration | 21 days of ketamine administration |
| Measures | Locomotor activity, stereotypic behaviors, forced swim test, elevated plus maze, biochemical assays, mitochondrial complexes assays |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine given for 21 days increased locomotor activity and stereotypic behaviors, increased immobility duration, and increased transfer latency, while weakening oxidative defense and mitochondrial function in mouse prefrontal cortex and hippocampus. Hesperidin and coenzyme Q10 each significantly reversed these behavioral, biochemical, and mitochondrial changes, with effects comparable to olanzapine; combining hesperidin with coenzyme Q10, or adding olanzapine, produced no significant additional benefit. The authors suggest hesperidin alone or with coenzyme Q10 may have neuroprotective effects against psychosis. |
Abstract
Psychosis 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. Ketamine (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. The 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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 2
- Effective action of silymarin against ketamine-induced schizophrenia in male mice: Insight into the biochemical and molecular mechanisms of action. Journal of Psychiatric Research November 1, 2024
- α-tocopherol alleviates ketamine toxicity in rat brain neurons. BMC Pharmacology and Toxicology January 30, 2026