title: Protective effect of betulin on cognitive decline in streptozotocin (STZ)-induced diabetic rats.
abstract: Betulin is extracted from birch tree bark and exerts diverse pharmacological activities. The present study was designed to investigate the protective effect of betulin (BE) on cognitive decline in streptozotocin (STZ)-induced diabetic rats. The diabetic model was built by streptozotocin (STZ) (30mg/kg, ip). After 4 weeks, the diabetic rats were treated with vehicle or BE (20mg/kg, 40mg/kg) for 4 weeks. The oral glucose tolerance (OGTT) and serum insulin were detected. Three days later, Morris water maze (MWM) test was used to evaluate memory function. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in hippocampus were examined. Inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in serum and hippocampus were measured. The protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NF-κB pathways-related molecules in hippocampus were examined. As a results, BE could improve glucose intolerance and modify basal learning performance. Treatment with BE significantly restored SOD activity and decreased MDA content in hippocampus. BE also markedly reduced the contents of inflammatory cytokines in serum and hippocampus. Furthermore, administration of BE effectively upregulated the expressions of Nrf2, HO-1 and blocked the phosphorylations of IκB, NF-κB. In summary, BE might exhibit protective effect on cognitive decline in STZ-induced diabetic rats through HO-1/Nrf-2/NF-κB pathway.
authors.affiliation: Central Laboratory, Nanjing Municipal Hospital of T.C.M., The Third Affiliated Hospital of Nanjing University of T.C.M., Nanjing 210001, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ma
authors.affiliation: Central Laboratory, Nanjing Municipal Hospital of T.C.M., The Third Affiliated Hospital of Nanjing University of T.C.M., Nanjing 210001, China. Electronic address: longhongyantcm@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Long
mesh_terms: D000818:Animals; D008297:Male; D051381:Rats; D060825:Cognitive Dysfunction / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000097:blood; D018782:Maze Learning / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood; D014315:Triterpenes / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D000094062:Betulinic Acid
chemical_list: D016207:Cytokines; D051547:Heme Oxygenase-1; D008315:Malondialdehyde; D016328:NF-kappa B; D013482:Superoxide Dismutase; D014315:Triterpenes; D051267:NF-E2-Related Factor 2; C002503:betulin; D000094062:Betulinic Acid
keywords: Betulin; Cognitive decline; HO-1/Nrf-2/NF-κB; STZ