Piperine restores streptozotocin-induced cognitive impairments: Insights into oxidative balance in cerebrospinal fluid and hippocampus

Behav Brain Res. 2018 Jan 30:337:131-138. doi: 10.1016/j.bbr.2017.09.031. Epub 2017 Sep 20.


Piperine has been shown to have antioxidant activity and a cognitive-enhancing effect following long-term oral administration. In a comparative study of memantine, the current investigation threw light on the cognitive benefits of piperine. Lipid peroxidation and the ferric reducing antioxidant power (FRAP) of cerebrospinal fluid (CSF) and hippocampus in streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type was measured. After reaching a criterion in a memory test, STZ-induced rats received piperine [2.5, 5, and 10mg/kg, intraperitoneally (i.p.)], vehicle, and memantine (10mg/kg, i.p.) for two weeks after the first STZ administration, or two weeks before and one week after, as a preventive approach. After the behavioral studies, samples were taken for biochemical and histological assays. An appropriate concentration of piperine (2.5mg/kg), on a daily basis, effectively increased the number of correct (non-repeated) arm entries and repressed reentry to a previously visited arm, in terms of reference errors as well as memantine (10mg/kg, i.p.), irrespective of the dose administered. The cognitive-enhancing effect induced by piperine at a relevant dose was simultaneous with CSF and hippocampal malonaldehyde decrement, and the redox balance was established to some extent by maintaining the FRAP levels of CSF near to those of the control. Similarly, the neuroprotective properties of piperine are in accordance with histopathological outcomes, which have shown an increased number of live cresyl violet (CV)-positive neurons in a dentate gyrus (DG) subregion. Therefore, the effects of piperine on the redox balance of CSF and hippocampal neurons may certainly contribute to the cognitive-enhancing activity of the drug.

Keywords: Alzheimer’s disease; Cerebrospinal fluid; Cognitive impairment; Oxidative stress; Piperine; Streptozotocin.

MeSH terms

  • Alkaloids / therapeutic use*
  • Analysis of Variance
  • Animals
  • Antibiotics, Antineoplastic / toxicity
  • Avoidance Learning / drug effects
  • Benzodioxoles / therapeutic use*
  • Cognition Disorders* / cerebrospinal fluid
  • Cognition Disorders* / chemically induced
  • Cognition Disorders* / drug therapy
  • Cognition Disorders* / pathology
  • Cytochrome P-450 Enzyme Inhibitors / therapeutic use*
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / cerebrospinal fluid*
  • Maze Learning / drug effects
  • Memantine / cerebrospinal fluid*
  • Memory, Short-Term / drug effects
  • Neurons / drug effects
  • Neurons / pathology
  • Piperidines / therapeutic use*
  • Polyunsaturated Alkamides / therapeutic use*
  • Rats
  • Rats, Wistar
  • Streptozocin / toxicity


  • Alkaloids
  • Antibiotics, Antineoplastic
  • Benzodioxoles
  • Cytochrome P-450 Enzyme Inhibitors
  • Piperidines
  • Polyunsaturated Alkamides
  • Malondialdehyde
  • Streptozocin
  • piperine
  • Memantine