title: Inhibitory effect of Thymus caramanicus Jalas on hyperglycemia-induced apoptosis in in vitro and in vivo models of diabetic neuropathic pain.
abstract: BACKGROUND
  Since Thymus caramanicus Jalas is used as a folk medicine for the treatment of rheumatism, skin disorders, bacterial infections and diabetes and it contain antioxidant agents, we decided to investigate the possible effects of Thymus caramanicus Jalas (TCJ) extract on in vitro and in vivo models of diabetic neuropathy.
  
  
  METHODS
  The high glucose-induced cell injury in Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick and rotarod treadmill assessments were used to determine nociceptive threshold and motor coordination. Cell viability was determined by MTT assay test. Western blotting was performed to measurement of apoptosis markers.
  
  
  RESULTS
  The data showed that elevation of glucose consecutively increases functional cell injury and apoptosis. Furthermore, diabetic rats developed thermal hyperalgesia and motor deficit. Activated caspase 3, cytochrome c release and Bax/Bcl-2 ratio were significantly increased in high glucose-treated PC12 cells and in spinal cord of diabetic animals. TCJ extract (60 and 80 µg/ml) attenuates high glucose-induced PC12 cells damage and apoptosis. In diabetic animals, TCJ extract at daily doses of 100 and 150 mg/kg ameliorated hyperalgesia and suppressed spinal apoptosis.
  
  
  CONCLUSIONS
  The data indicate that TCJ extract has neuroprotective effects against high glucose-induced neural damage. These protective effects are mediated, at least in part, through attenuation of neural apoptosis and suggest therapeutic potential of TCJ extract in amelioration of diabetic neuropathy.
authors.affiliation: Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Department of Biology, PayamNoor University, 19395-4697 Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hajializadeh
authors.affiliation: Department of Biology, PayamNoor University, 19395-4697 Tehran, Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Nasri
authors.affiliation: Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khoramabad, Iran.
authors.forename: Ayat
authors.initials: A
authors.lastname: Kaeidi
authors.affiliation: Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Sheibani
authors.affiliation: Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khoramabad, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Rasoulian
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, P.O. Box 76135-133, Kerman, Iran. Electronic address: semahani@yahoo.com.
authors.forename: Saeed
authors.initials: S
authors.lastname: Esmaeili-Mahani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D016716:PC12 Cells; D010147:Pain Measurement; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D046930:Thymus Plant; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D001786:Blood Glucose; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Apoptosis; Diabetic neuropathy; PC12 cells; Pain; Rats; Thymus caramanicus Jalas