title: Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression.
abstract: OBJECTIVE
  Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats.
  
  
  METHODS
  Rats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain.
  
  
  RESULTS
  Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone.
  
  
  CONCLUSIONS
  The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Rinwa
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Sukant
authors.initials: S
authors.lastname: Garg
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005518:Food Preferences; D007103:Immobilization; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009830:Olfactory Bulb / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013395:Sucrose; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D019208:Brain-Derived Neurotrophic Factor; D045222:Electron Transport Chain Complex Proteins; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; D013395:Sucrose; D053148:Caspase 3; D003474:Curcumin; C008922:piperine; D003345:Corticosterone