Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer's disease

J Nutr Biochem. 2019 Aug:70:147-155. doi: 10.1016/j.jnutbio.2019.05.009. Epub 2019 May 24.


Piperine, the major alkaloid constituent of black pepper, has been reported to possess a wide range of pharmacological effects on the central nervous system, including antidepressant, anticonvulsant and anti-ischemic activities. In the present study, we aimed to investigate the therapeutic potential and neuroprotective mechanisms of piperine in an experimental mouse model of sporadic Alzheimer's disease (sAD) induced by intracerebroventricular (ICV) infusion of streptozotocin (STZ). STZ was infused bilaterally at a dose of 1.5 mg/kg/day on day 1 and day 3. From day 8, piperine (2.5-10 mg/kg body weight) was administered intraperitoneally once daily for 15 consecutive days. The locomotor activity and cognitive performance of mice were evaluated using open field test and Morris water maze test, respectively. On day 23, all animals were sacrificed, and the hippocampus was used for biochemical, neurochemical and neuroinflammatory determinations. Our data revealed that the ICV-STZ-infused sAD mouse showed an increased oxidative-nitrosative stress, an altered neurotransmission and an elevated neuroinflammation in hippocampus, as well as significant cognitive deficits. All these alterations can be ameliorated by piperine in a dose-dependent manner. In summary, our findings predict a therapeutic potential of piperine against cognitive deficits in sAD mouse. This effect might be due to its abilities to ameliorate oxidative-nitrosative stress, restore neurotransmission and reduce neuroinflammation.

Keywords: Cognition; Neuroinflammation; Neurotransmission; Oxidative stress; Piperine; Sporadic Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Animals
  • Benzodioxoles / pharmacology*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Inflammation
  • Infusions, Intraventricular
  • Male
  • Maze Learning
  • Memory Disorders
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Nitrogen / chemistry
  • Oxidative Stress
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Streptozocin


  • Alkaloids
  • Benzodioxoles
  • Neuroprotective Agents
  • Piperidines
  • Polyunsaturated Alkamides
  • Streptozocin
  • Nitrogen
  • piperine