title: Acerogenin A from Acer nikoense Maxim Prevents Oxidative Stress-Induced Neuronal Cell Death through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse Hippocampal HT22 Cell Line.
abstract: Oxidative cell damage contributes to neuronal degeneration in many central nervous system (CNS) diseases such as Parkinson's disease, Alzheimer's disease, and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a key role in the pathogenesis of neuronal diseases. The stem bark of Acer nikoense Maxim (Aceraceae) is indigenous to Japan; it has been used in folk medicine as a treatment of hepatic disorders and eye diseases. Acerogenin A, a natural compound isolated from Japanese folk medicine A. nikoense, showed neuroprotective effects and reactive oxygen species (ROS) reduction on glutamate-induced neurotoxicity by inducing the expression of HO-1 in mouse hippocampal HT22 cells. Furthermore, acerogenin A caused the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and the activation of the PI3K/AKT signaling pathways. In this study, we demonstrated that acerogenin A effectively prevents glutamate-induced oxidative damage, and HO-1 induction via PI3K/Akt and Nrf2 pathways appears to play a key role in the protection of HT22 cells. Therefore, this study implies that the Nrf2/HO-1 pathway represents a biological target and that acerogenin A might be a candidate for the prevention of neurodegeneration.
authors.affiliation: Department of Biomedical Chemistry, College of Health and Biomedical Science, Konkuk University, Chung-Ju 380-701, Korea. dslee@kku.ac.kr.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan. bycha@isc.chubu.ac.jp.
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Cha
authors.affiliation: Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan. jwoo@isc.chubu.ac.jp.
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. yckim@wku.ac.kr.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Inha University School of Medicine, Incheon 400-712, Korea. juhjang@inha.ac.kr.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D036381:Diarylheptanoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010647:Phenyl Ethers / Q000302:isolation & purification / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D000097566:Cyclophanes
chemical_list: D036381:Diarylheptanoids; D018698:Glutamic Acid; D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D010647:Phenyl Ethers; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C495636:Nfe2l2 protein, mouse; C557988:acerogenin A; D000097566:Cyclophanes; C496542:Hmox1 protein, mouse
keywords: acerogenin A; heme oxygenase-1; mouse hippocampal HT22 cells; neuro-protective effects; nuclear factor-E2-related factor 2