Neuroprotective effects of the ethanol stem bark extracts of Terminalia ivorensis in ketamine-induced schizophrenia-like behaviors and oxidative damage in mice

Pharm Biol. 2016 Dec;54(12):2871-2879. doi: 10.1080/13880209.2016.1190382. Epub 2016 Jun 2.

Abstract

Context: Schizophrenia is a heterogenous neurological disorder, which has been hypothetically linked to oxidative imbalance and associated behavioral perturbations. Preliminary evidence from animal models predictive of human psychosis suggests that Terminalia ivorensis A. Chev. (Combretaceae) has antipsychotic-like activity in mice.

Objective: This study investigates the neuroprotective property of the ethanol stem bark extracts of T. ivorensis (EETI) in reversal treatment of ketamine-induced schizophrenia-like behaviors and oxidative alteration in adult male Swiss albino mice.

Materials and methods: Animals were divided into six treatment groups (n = 5). Animals received distilled water or ketamine (20 mg/kg) once daily intraperitoneally (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with EETI (125, 250 or 500 mg/kg), risperidone (RIS) or vehicle orally once daily. Behaviors related to positive (locomotor activity) and cognitive (Y maze) symptoms of schizophrenia were assessed. Glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, including malondialdehyde (MDA) concentration were measured in mice whole brains.

Result: The LD50 of EETI was 2236.06 mg/kg, p.o. body weight. EETI (125, 250 or 500 mg/kg, p.o.) demonstrated significant (p < 0.05) inhibition of ketamine-induced hyperlocomotion and cognitive dysfunction. The extract decreased MDA concentration (39.0, 62.6 and 67.5%) in a dose-dependent manner. Moreover, EETI significantly (p < 0.05) reversed the depletion of GSH, and increased activities of SOD and CAT in brain tissues.

Discussion and conclusion: These findings suggest that EETI probably exert its antipsychotic-like activity, via a neuroprotective compensatory mechanism of action, and as such, could be relevant in the management of schizophrenia.

Keywords: Antipsychotics; antioxidants; neuroprotection; psychosis.

MeSH terms

  • Animals
  • Antipsychotic Agents / isolation & purification
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology
  • Ethanol / therapeutic use
  • Ketamine / toxicity*
  • Male
  • Mice
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Plant Bark
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Stems
  • Schizophrenia / chemically induced
  • Schizophrenia / metabolism
  • Schizophrenia / prevention & control*
  • Terminalia*
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Neuroprotective Agents
  • Plant Extracts
  • Ethanol
  • Ketamine