title: Naringenin confers protection against oxidative stress through upregulation of Nrf2 target genes in cardiomyoblast cells.
abstract: Cardiovascular diseases are the major health concern and the leading cause of death. Numerous studies have shown that oxidative stress stimuli have been incriminated in the pathogenesis of both acute and chronic heart disease. Though it is well known that bioflavonoids protect cells against reactive oxygen species (ROS)-induced damage, the molecular mechanisms involved are uncertain. Understanding the possible intracellular signaling pathways triggered by flavonoids will help to overcome the cardiac diseases resulting from oxidative stress. In the present study, we investigated whether naringenin (NGN) supplementation would improve the antioxidant defence under oxidative stress through the activation of Nrf2 signaling in cultured cardiomyoblast. NGN pretreatment significantly reduced stress-mediated apoptotic cell death and lipid peroxidation and showed increased level of reduced glutathione in H2O2-treated cardiomyoblast. In addition, NGN inhibited the production of NO and trigged the synthesis of antioxidant marker enzymes. Gene expression studies revealed that NGN upregulated the transcription of Akt and downregulated NF-κB and Caspase 3 genes. Notably, transcription of Nrf2 and its target genes was also upregulated. Taken together, the present study revealed that NGN elicits potent cytoprotective effect against oxidative stress by regulating Nrf2 and its target genes. In conclusion, the present work suggests that improving Nrf2 signaling by NGN supplementation would be a rational approach to facilitate ROS detoxification by augmenting both expression and activity of phase II detoxification enzymes for the alleviation of cardiac complications.
authors: Molecular Cardiology Unit, Department of Biochemistry (Center for Excellence in Genomic Sciences), School of Biological Sciences, Madurai Kamaraj University, Madurai, 625 021, Tamilnadu, India.
authors: Tharmarajan
authors: T
authors: Ramprasath
authors: Manivasagam
authors: M
authors: Senthamizharasi
authors: Varadaraj
authors: V
authors: Vasudevan
authors: Sundaresan
authors: S
authors: Sasikumar
authors: Subramani
authors: S
authors: Yuvaraj
authors: Govindan Sadasivam
authors: GS
authors: Selvam
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D044950:Flavanones / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D017931:DNA Primers; D044950:Flavanones; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C005273:naringenin