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.