title: Antioxidant and free radical scavenging potential of yakuchinone B derivatives in reduction of lipofuscin formation using H2O2-treated neuroblastoma cells.
abstract: BACKGROUND
  The progressive accumulation of misfolded and aggregated proteins in neurons is an accepted mechanism in aging. Overproduction of reactive oxygen species (ROS), referred to as oxidative stress, is currently believed to play a pivotal role in this process. Lipofuscin as a histological index of aging results from cross-links between oxidized proteins and lipids. Therefore, to attenuate lipofuscin formation, it would be logical to use exogenous natural or synthetic antioxidants. Yakuchinone B (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenylhept-1-en-3-one) is a component of Alpinia oxyphylla seeds with established antioxidant activity.
  
  
  METHODS
  To evaluate the neuroprotective roles of yakuchinone B (JC6) and its structural analogues (JC1-JC5), the free radical scavenging capabilities of yakuchinone B derivatives were studied in terms of cell viability, apoptosis, cells ROS content, catalase (CAT) and superoxide dismutase (SOD) activity and the intracellular lipofuscin content in SK-N-MC cells exposed to H2O2. The level of MDA (malondialdehyde), as an index of lipid peroxidation and acid phosphatase activity were also measured.
  
  
  RESULTS
  Our results indicated that derivatives especially JC4, JC5 and JC6 decreased the extent of apoptosis and ROS level, while they increased the activities of SOD and CAT in drug-pretreated cells as compared to H2O2-treated cells. A clear relationship between the structure and antioxidant activities of these compounds was established. In addition, JC4, JC5 and JC6 were capable of down-regulating the formation of MDA and lipofuscin.
  
  
  CONCLUSIONS
  Our results indicated that free radicals play significant roles in lipofuscin formation and cellular aging which can be attenuated by yakuchinone B derivatives.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, P. O. Box 13145-1384, Tehran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Bayati
authors.forename: Razieh
authors.initials: R
authors.lastname: Yazdanparast
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry; D036381:Diarylheptanoids / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D008062:Lipofuscin / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology*; D020011:Protective Agents / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D036381:Diarylheptanoids; D016166:Free Radical Scavengers; D008062:Lipofuscin; D020011:Protective Agents; C121978:yakuchinone B; D002599:Chalcone; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D000135:Acid Phosphatase