title: The Neuroprotective Effects of Ratanasampil on Oxidative Stress-Mediated Neuronal Damage in Human Neuronal SH-SY5Y Cells.
abstract: We previously found that Ratanasampil (RNSP), a traditional Tibetan medicine, improves the cognitive function of mild-to-moderate AD patients living at high altitude, as well as learning and memory in an AD mouse model (Tg2576); however, mechanism underlying the effects of RNSP is unknown. In the present study, we investigated the effects and molecular mechanisms of RNSP on oxidative stress-induced neuronal toxicity using human neuroblastoma SH-SY5Y cells. Pretreatment with RNSP significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity of SH-SY5Y cells in a dose-dependent manner (up to 60 μg/mL). Furthermore, RNSP significantly reduced the H2O2-induced upregulation of 8-oxo-2'-deoxyguanosine (8-oxo-dG, the oxidative DNA damage marker) but significantly reversed the expression of repressor element-1 silencing transcription factor (REST) from H2O2 associated (100 μM) downregulation. Moreover, RNSP significantly attenuated the H2O2-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) in SH-SY5Y cells. These observations strongly suggest that RNSP may protect the oxidative stress-induced neuronal damage that occurs through the properties of various antioxidants and inhibit the activation of MAPKs. We thus provide the principle molecular mechanisms of the effects of RNSP and indicate its role in the prevention and clinical management of AD.
authors.affiliation: Institution of Geriatric Qinghai Provincial Hospital, Xining 810007, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Zhou
authors.identifier: 0000-0002-4910-9037
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.affiliation: Kinsmen Laboratory of Neurological Research, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1W5.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
authors.affiliation: Hospital Infection Management Office, Hospital of Xinjiang Production and Construction Corps, Urumqi, Xinjiang 830002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Institution of Geriatric Qinghai Provincial Hospital, Xining 810007, China.
authors.forename: Shizheng
authors.initials: S
authors.lastname: Wu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D038861:Medicine, Tibetan Traditional; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D003849:Deoxyguanosine