title: Naringin ameliorates memory deficits in experimental paradigm of Alzheimer's disease by attenuating mitochondrial dysfunction.
abstract: BACKGROUND
  Mitochondrial dysfunction has been well documented in age related disorders like Alzheimer's disease. Alterations in mitochondrial membrane potential lead to neuronal death by excessive generation of free radicals, inflammatory cytokines, and excitotoxins. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental model of Alzheimer's disease. Naringin is a potent antioxidant, which can cross the blood brain barrier protecting brain tissue and modulating brain chemistry.
  
  
  OBJECTIVE
  The present study was designed to evaluate the effect of naringin, in ICV STZ-induced mitochondrial dysfunction and memory loss in rats.
  
  
  METHODS
  Streptozotocin (3mg/kg, ICV) was injected bilaterally in two divided doses on first and third day followed by treatment with different doses of naringin (50, 100 and 200mg/kg; p.o.) for twenty one days. Behavioral alterations were monitored using Morris water maze paradigm and elevated plus maze test. Animals were sacrificed to evaluate various biochemical and mitochondrial parameters in brain. Rivastigmine was used as a standard drug.
  
  
  RESULTS
  ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced oxidative-nitrosative stress, altered acetylcholinesterase and mitochondrial enzyme activities in cerebral cortex and hippocampus of rats brain along with significantly increased brain TNF-α and IL-1β levels. Chronic treatment with naringin dose dependently restored cognitive deficits in ICV-STZ rat along with mitigation of mitochondrial dysfunction mediated oxido-nitrosative stress and cytokine release.
  
  
  CONCLUSIONS
  Our findings demonstrate that naringin ameliorates mitochondrial dysfunction mediated oxido-nitrosative stress and inflammatory surge in ICV-STZ rats.
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160 014 India.
authors.forename: Anand Kamal
authors.initials: AK
authors.lastname: Sachdeva
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160 014 India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Kuhad
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160 014 India. Electronic address: dr_chopra_k@yahoo.com.
authors.forename: Kanwaljit
authors.initials: K
authors.lastname: Chopra
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D044950:Flavanones; C005274:naringin
keywords: Cognitive impairment; ICV-STZ; IL-1β; Mitochondrial dysfunction; Naringin; TNF-α