title: Neuroprotective effects of phytosterols and flavonoids from Cirsium setidens and Aster scaber in human brain neuroblastoma SK-N-SH cells.
abstract: OBJECTIVE
  We investigated the neuroprotective effects and action mechanism of three major compounds [daucosterol (Dau), pectolinarin (Pec), and astragalin (Ast)] isolated from edible plants against H2O2-induced cell death of human brain neuroblastoma SK-N-SH cells.
  
  
  METHODS
  Cytotoxicity was determined by MTT and lactate dehydrogenase (LDH) assays. Apoptotic cell death was monitored by annexin V-FITC/PI double staining and by TUNEL assay. The formation of reactive oxygen species (ROS), expression of antioxidant enzymes and phosphorylation of mitogen-activated protein kinase (MAPK) were determined by 2,7-dichlorofluorescein diacetate (DCF-DA) assay, RT-PCR, and western blotting, respectively.
  
  
  RESULTS
  The ethyl acetate fractions from Cirsium setidens (CSEA) and Aster scaber (ASEA) showed neuroprotective effects in SK-N-SH cells. The phytochemicals were isolated from CSEA and ASEA and identified by spectral analyses, as β-sitosterol, Dau, Pec, Ast, or isoquercitrin. Pretreatment with Dau, Pec, or Ast showed protective effects against H2O2-induced cell death and inhibited ROS generation by oxidative stress. HO-1 mRNA and protein levels were increased by the presence of H2O2 and were further elevated by pretreatment with Dau and Ast. Dau pretreatment resulted in further increases of H2O2-induced enhancement in levels of CAT and SOD2. Pretreatment with Dau, Pec, and Ast inhibited phosphorylation of MAPK, such as extracellular protein regulated protein kinase, p38, and c-Jun N-terminal kinase by H2O2.
  
  
  CONCLUSIONS
  Dau exerts its neuroprotective effects by down regulation of MAPK pathways and upregulation of the HO-1, CAT and SOD2 antioxidant genes and is associated with reduced oxidative stress in SK-N-SH cells.
authors.affiliation: Department of Food Science and Nutrition, Gwangju University, Gwangju 61743, Republic of Korea.
authors.forename: Mi Ja
authors.initials: MJ
authors.lastname: Chung
authors.affiliation: Department of Integrative Plant Science, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, The Catholic Institute for Advanced Biomaterials, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Park
authors.affiliation: Department of Biotechnology, The Catholic Institute for Advanced Biomaterials, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Gwangju University, Gwangju 61743, Republic of Korea. Electronic address: khkwon@gwangju.ac.kr.
authors.forename: Ki Han
authors.initials: KH
authors.lastname: Kwon
mesh_terms: D031173:Aster Plant; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D031180:Cirsium; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D010840:Phytosterols / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; D010840:Phytosterols; D010936:Plant Extracts
keywords: Aster scaber; Cirsium setidens; Daucosterol; Neuroprotective effects; Oxidative stress