title: Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice.
abstract: Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer's disease (AD). The aims of the present study were to determine and explore the antioxidant nature and potential mechanism of vanillic acid (VA) in Aβ1-42-induced oxidative stress and neuroinflammation mediated cognitive impairment in mice. An intracerebroventricular (i.c.v.) injection of Aβ1-42into the mouse brain triggered increased reactive oxygen species (ROS) levels, neuroinflammation, synaptic deficits, memory impairment, and neurodegeneration. In contrast, the i.p. (intraperitoneal) administration of VA (30 mg/kg, for 3 weeks) after Aβ1-42-injection enhanced glutathione levels (GSH) and abrogated ROS generation accompanied by an induction of the endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) via the activation of Akt and glycogen synthase kinase 3β (GSK-3β) in the brain mice. Additionally, VA treatment decreased Aβ1-42-induced neuronal apoptosis and neuroinflammation and improved synaptic and cognitive deficits. Moreover, VA was nontoxic to HT22 cells and increased cell viability after Aβ1-42exposure. To our knowledge, this study is the first to reveal the neuroprotective effect of VA against Aβ1-42-induced neurotoxicity. Our findings demonstrate that VA could potentially serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.
authors.affiliation: Department of Biology, Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Faiz Ul
authors.initials: FU
authors.lastname: Amin
authors.affiliation: Department of Biology, Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Shahid Ali
authors.initials: SA
authors.lastname: Shah
authors.affiliation: Department of Biology, Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D060825:Cognitive Dysfunction / Q000188:drug therapy; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D008569:Memory Disorders; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014641:Vanillic Acid / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D014641:Vanillic Acid