title: Parthenolide, an NF-κB Inhibitor Ameliorates Diabetes-Induced Behavioural Deficit, Neurotransmitter Imbalance and Neuroinflammation in Type 2 Diabetes Rat Model.
abstract: Diabetes is associated with behavioural and neurochemical alterations. In this manuscript, we are reporting the beneficial effects of parthenolide, an NF-κB inhibitor on behavioural and neurochemical deficits in type 2 diabetic rat model. Diabetes was induced by high-fat diet followed by low dose of streptozotocin (35 mg/kg). Elevated plus maze, open-field, MWM and passive avoidance test paradigm were used to assess behavioural and cognitive deficits. Three-week treatment of parthenolide (0.25 and 0.50 mg/kg; i.p.) attenuated diabetes-induced alteration in cognitive function in Morris water maze and passive avoidance test. Anxiety-like behaviour was also reduced by parthenolide treatment. Moreover, TNF-α and IL-6 levels were significantly decreased in cortex and hippocampus of parthenolide-treated rats. Three-week parthenolide treatment also toned down the alteration of GABA and glutamate homoeostasis. Results of this study corroborate the involvement of neuroinflammation in the development of behavioural and neurochemical deficits in diabetic animals and point towards the therapeutic potential of parthenolide in diabetes-induced alteration of learning, memory and anxiety behaviour.
authors.affiliation: Molecular Neuropharmacology Lab., Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar, Punjab, 160062, India.
authors.forename: Pragyanshu
authors.initials: P
authors.lastname: Khare
authors.affiliation: Molecular Neuropharmacology Lab., Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar, Punjab, 160062, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Datusalia
authors.affiliation: Molecular Neuropharmacology Lab., Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar, Punjab, 160062, India. sssharma@niper.ac.in.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Sharma
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D001923:Brain Chemistry / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D059305:Diet, High-Fat / Q000009:adverse effects; D005106:Exploratory Behavior / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis; D018782:Maze Learning / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000110:Acetylcholinesterase; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D016328:NF-kappa B; D018377:Neurotransmitter Agents; D012717:Sesquiterpenes; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha; C002669:parthenolide
keywords: Anxiety-like behaviour; Cognitive deficits; GABA; Glutamate; Neuroinflammation; Parthenolide; Type 2 diabetes