title: Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies.
abstract: OBJECTIVE
  Since the leaves of olive have been recommended in the literature as a remedy for the treatment of diabetes and they also contain antioxidant agents, we decided to investigate the possible effects of olive leaf extract (OLE) on in vitro and in vivo models of diabetic pain neuropathy.
  
  
  METHODS
  The high glucose-induced cell damage in naive and NGF-treated Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick test was used to access nociceptive threshold. Cell viability was determined by MTT assay. Biochemical markers of neural apoptosis were evaluated using immunoblotting.
  
  
  RESULTS
  We found that elevation of glucose (4 times of normal) sequentially increases functional cell damage and caspase-3 activation in NGF-treated PC12 cells. Incubation of cells with OLE (200, 400 and 600 μg/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathic pain which was evident from decreased tail-flick latency (thermal hyperalgesia). Activated caspase 3 and Bax/Bcl2 ratio were significantly increased in spinal cord of diabetic animals. OLE treatment (300 and 500 mg/kg per day) ameliorated hyperalgesia, inhibited caspase 3 activation and decreased Bax/Bcl2 ratio. Furthermore, OLE exhibited potent DPPH free radical scavenging capacity.
  
  
  CONCLUSIONS
  The results suggest that olive leaf extract inhibits high glucose-induced neural damage and suppresses diabetes-induced thermal hyperalgesia. The mechanisms of these effects may be due, at least in part, to reduce neuronal apoptosis and suggest therapeutic potential of olive leaf extract in attenuation of diabetic neuropathic pain.
authors.affiliation: Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Ayat
authors.initials: A
authors.lastname: Kaeidi
authors.forename: Saeed
authors.initials: S
authors.lastname: Esmaeili-Mahani
authors.forename: Vahid
authors.initials: V
authors.lastname: Sheibani
authors.forename: Mehdi
authors.initials: M
authors.lastname: Abbasnejad
authors.forename: Bahram
authors.initials: B
authors.lastname: Rasoulian
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hajializadeh
authors.forename: Samira
authors.initials: S
authors.lastname: Afrazi
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D031658:Olea; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008517:Phytotherapy; D010851:Picrates / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000700:Analgesics; D000975:Antioxidants; D001713:Biphenyl Compounds; D001786:Blood Glucose; D016166:Free Radical Scavengers; D010851:Picrates; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C004931:1,1-diphenyl-2-picrylhydrazyl; D053148:Caspase 3