Memory Enhancing Effect of Black Pepper in the AlCl3 Induced Neurotoxicity Mouse Model is Mediated Through Its Active Component Chavicine

Curr Pharm Biotechnol. 2016;17(11):962-73. doi: 10.2174/1389201017666160709202124.


Black pepper (Piper nigrum Linn.) has vital pharmacological properties with profound effects on central nervous system. Neurotoxic agents like Aluminum Chloride (AlCl3) cause the oxidative stress and result in improper processing of amyloid proteins leading to accumulation of amyloid β plaques.

Aim: The study aimed to explore the neuroprotective potential of black pepper (BP) extract (12.5mg/kg/day) on memory enhancement and its effect on expression of amyloid precursor protein (APP) isoforms (APP770 and APP695) in AlCl3 induced neurotoxicity (250mg/kg) mouse model. The study included the isolation and identification of pure compound from BP (chavicine) which was found pharmacologically active.

Methods: Morris water maze test, elevated plus maze, fear conditioning, context and cue dependent test and social preference tests were performed to investigate the learning and memory. Gene expression (APP isoforms) and in-vitro and ex-vivo DPPH free radical scavenging activity were performed to evaluate the role of BP.

Results: BP significantly improved memory in AlCl3 induced neurotoxicity mouse model along with effectively decreasing the expression of APP770 (amyloidogenic) isoform and improved level of APP695 (non-amyloidogenic) in hippocampus, amygdala and cortex. Fear extinction learning was considerably improved in BP treated group (7.83±2.03) than AlCl3 induced neurotoxicity group (39.75±4.25). In the hippocampus, BP significantly reduced the expression of APP770 (0.37±0.05) as compared to AlCl3 induced neurotoxicity group (0.72±0.06), and effectively increased (34.80±1.39) the percentage inhibition of DPPH free radicals as compared to AlCl3 induced neurotoxicity group (14±2.68).

Conclusion: The study revealed that BP improves memory and chavicine is a lead compound producing pharmacological effects of BP.

MeSH terms

  • Aluminum Chloride
  • Aluminum Compounds / toxicity*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Chlorides / toxicity*
  • Disease Models, Animal*
  • Fear / drug effects
  • Fear / physiology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory / drug effects*
  • Memory / physiology
  • Mice
  • Mice, Inbred BALB C
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / metabolism
  • Nootropic Agents / isolation & purification
  • Nootropic Agents / pharmacology
  • Nootropic Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Piper nigrum*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use


  • Aluminum Compounds
  • Amyloid beta-Peptides
  • Chlorides
  • Nootropic Agents
  • Plant Extracts
  • Aluminum Chloride