title: Promising effects on ameliorating mitochondrial function and enhancing Akt signaling in SH-SY5Y cells by (M)-bicelaphanol A, a novel dimeric podocarpane type trinorditerpene isolated from Celastrus orbiculatus.
abstract: Oxidative stress plays an important role in the pathological processes of various neurodegenerative diseases. In this study, we investigated the neuroprotective effects of (M)-bicelaphanol A, which has been the first dimeric podocarpane type trinorditerpene isolated from Celastrus orbiculatus, against hydrogen peroxide (H2O2)-induced injury in human SH-SY5Y neuroblastoma cells. Our study showed that cells pretreated with (M)-bicelaphanol A significantly attenuated H2O2-induced cell viability reduction and cell apoptosis. These neuroprotective effects of (M)-bicelaphanol A were associated with a reduction of reactive oxygen species and an increase in the level of adenosine triphosphate. In addition, (M)-bicelaphanol A pretreatment markedly increased the phosphorylation level of Akt in SH-SY5Y cells. In conclusion, our results for the first time demonstrate that the protection of (M)-bicelaphanol A on SH-SY5Y cells against H2O2-induced oxidative stress may attribute, at least partially, to its attenuation of mitochondrial dysfunction and activation of Akt signaling pathway. Above results shed more light on the molecular mechanisms involved in the neuroprotective effects of (M)-bicelaphanol A, which could be a potential drug candidate for the treatment of oxidative stress-associated neurodegenerative diseases.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Xu Jie
authors.initials: XJ
authors.lastname: Wang
authors.forename: Luo Yi
authors.initials: LY
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Xi Can
authors.initials: XC
authors.lastname: Tang
authors.forename: Wei Min
authors.initials: WM
authors.lastname: Zhao
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000378:metabolism; D031247:Celastrus / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents; D018384:Oxidative Stress; D010766:Phosphorylation; D010851:Picrates / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C582699:(M)-bicelaphanol A; D001713:Biphenyl Compounds; D004224:Diterpenes; D018696:Neuroprotective Agents; D010851:Picrates; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D051057:Proto-Oncogene Proteins c-akt
keywords: (M)-bicelaphanol A; 1,1-diphenyl-2-picrylhydrazyl; 2′,7′-dichlorodihydrofluorescein diacetate; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; AD; ATP; Alzheimer's disease; Apoptosis; Celastrus orbiculatus; DMEM; DMSO; DPPH; Dulbecco's modified Eagle's medium; FBS; H(2)DCFDA; H(2)O(2); Hydrogen peroxide; MTT; Mitochondria; Neurodegenerative disease; Oxidative stress; PI; PS; ROS; adenosine triphosphate; dimethylsulfoxide; fetal bovine serum; hydrogen peroxide; phosphatidylserine; propidium iodide; reactive oxygen species