Piperine potentiates the protective effects of curcumin against chronic unpredictable stress-induced cognitive impairment and oxidative damage in mice

Brain Res. 2012 Dec 7;1488:38-50. doi: 10.1016/j.brainres.2012.10.002. Epub 2012 Oct 23.


Life event stressors are the major vulnerability factors for the development of cognitive disorders. A vital therapeutic for stress related disorders is curcumin, derived from curry spice turmeric. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study was designed to investigate the effect of curcumin and its co-administration with piperine against chronic unpredictable stress (CUS)-induced cognitive impairment and oxidative stress in mice. Male Laca mice were subjected to undergo a battery of stressors for a period of 28 days. Vehicle/drugs were administered daily 30mins before CUS procedure. Chronic stress significantly impaired memory performance (delayed latency time to reach platform in Morris water maze as well as to reach closed arm in elevated plus maze test) and decreased locomotor activity along with sucrose consumption. Further, there was a significant impairment in oxidative parameters (elevated malondialdehyde, nitrite concentration and decreased reduced glutathione, catalase levels) and mitochondrial enzyme complex activities, along with raised acetylcholinesterase and serum corticosterone levels. Chronic treatment with curcumin (200 and 400mg/kg, p.o.) significantly improved these behavioral and biochemical alterations, restored mitochondrial enzyme complex activities and attenuated increased acetylcholinesterase and serum corticosterone levels. In addition, co-administration of piperine (20mg/kg; p.o.) with curcumin (100 and 200mg/kg, p.o.) significantly elevated the protective effect as compared to their effects alone. The results clearly suggest that piperine enhanced the bioavailability of curcumin and potentiated its protective effects against CUS induced cognitive impairment and associated oxidative damage in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Benzodioxoles / pharmacology*
  • Chronic Disease
  • Cognition Disorders / metabolism
  • Cognition Disorders / prevention & control*
  • Corticosterone / blood
  • Curcumin / pharmacology*
  • Cytochrome P-450 Enzyme Inhibitors
  • Dietary Sucrose / pharmacology
  • Drug Synergism
  • Food Preferences / drug effects
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred Strains
  • Mitochondria / drug effects
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / metabolism
  • Uncertainty


  • Alkaloids
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzodioxoles
  • Cytochrome P-450 Enzyme Inhibitors
  • Dietary Sucrose
  • Neuroprotective Agents
  • Piperidines
  • Polyunsaturated Alkamides
  • Curcumin
  • piperine
  • Corticosterone