title: Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice.
abstract: Evidence suggests that obesity-induced cognitive impairments are driven by in brain inflammatory responses and inflammation-mediated brain insulin resistance. Ursolic acid (UA), a triterpenoid compound, has many important biological functions, including antioxidant and anti-inflammatory activities. Here, we evaluated the effect of UA on cognitive impairment induced by a high-fat diet (HFD), and we explored the potential mechanisms mediating this effect. Results showed that UA administration significantly improved the behavioral performance of C57/BL6J mice fed a HFD in both the step-through test and the Morris water maze task. These results were associated with the inhibition of endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory signaling and the restoration of insulin signaling and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. UA administration also increased memory-related protein expression in the hippocampus of mice given a HFD. However, the neuroprotective effects of UA were blocked by an intracerebroventricular (i.c.v.) injection of PI-103, a specific PI3K 110α inhibitor. These results suggest that UA may be a potent candidate for the prevention and treatment of cognitive deficits caused by type 2 diabetes.
authors.affiliation: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Wu
authors.forename: Yuan-lin
authors.initials: YL
authors.lastname: Zheng
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.forename: Zi-feng
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Shan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects; D051550:I-kappa B Kinase / Q000502:physiology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D014315:Triterpenes / Q000627:therapeutic use*; D000097245:Ursolic Acid
chemical_list: D016861:Cyclooxygenase Inhibitors; D004041:Dietary Fats; D051550:I-kappa B Kinase; D007328:Insulin; D016328:NF-kappa B; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D058570:TOR Serine-Threonine Kinases; D014315:Triterpenes; D000097245:Ursolic Acid; C491411:Socs3 protein, mouse; C546843:mTOR protein, mouse; C516609:Ptpn1 protein, mouse