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K. L. Seanor, J. V. Cross, S. M. Nguyen, M. Yan and D. J. Templeton, “Reactive Quinines Differentially Regulates SAPK/JNK and p38/mHOG Stress Kinases,” Antioxidants and Redox Signaling, Vol. 5, No. 1, 2003, pp. 103-113.

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• TITLE: Protective Effects of Flavonoid Baicalein against Menadione-Induced Damage in SK-N-MC Cells

  AUTHORS: Maryam Moslehi, Razieh Yazdanparast

  KEYWORDS: Aging; Baicalein; Lipofuscin; Menadione; Neurodegenerative Disease; Oxidative Stress

  JOURNAL NAME: CellBio, Vol.2 No.2, June 4, 2013

  ABSTRACT: Oxidative damage and redox metal homeostasis loss are two contributing factors in brain aging and widely distributed neurodegenerative diseases. Oxidative species in company with excessive amounts of intracellular free iron result in Fenton-type reaction with subsequent production of highly reactive hydroxyl radicals which initiate peroxidation of biomolecules and further formation of non-degradable toxic pigments called lipofuscin that amasses in long-lived postmitotic cells such as neurons. Dietary flavonoid baicalein can counteract the detrimental consequences through exertion of a multiplicity of protective actions within the brain including direct ROS scavenging activity and iron chelation. In this study, we evaluated the neuroprotective effects of baicalein in menadione (superoxide radical generator)-treated SK-N-MC neuroblastoma cell line. Our results showed that treatment of cells with menadione led to lipofuscin formation due to elevated intracellular iron contents and accumulation of oxidative products such as MDA and PCO. Also, menadione caused apoptotic cell death in SK-N-MC cells. However, pretreatment with baicalein (40 μM) reversed the harmful effects by chelating free iron and preventing biomolecules peroxidations. Moreover, baicalein prevented cell death through modulation of key molecules in apoptotic pathways including suppression of Bax and caspase-9 activities and induction of bcl2 expression. Key structural features such as presence of hydroxyl groups and iron-binding motifs in baicalein make it the appropriate candidate in antioxidant-based therapy in age-related neurodegenerative diseases.