PMID- 25058919 OWN - NLM STAT- MEDLINE DCOM- 20141124 LR - 20231213 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 113 IP - 1-2 DP - 2014 Sep 15 TI - Rosmarinic acid mediated neuroprotective effects against H2O2-induced neuronal cell damage in N2A cells. PG - 7-13 LID - S0024-3205(14)00619-5 [pii] LID - 10.1016/j.lfs.2014.07.010 [doi] AB - AIMS: Oxidative stress plays a key role in several ailments including neurodegenerative conditions. The aim of the study was to demonstrate the effect of rosmarinic acid (RA) in preventing oxidative stress related death of neuronal cell lines. MAIN METHODS: In the present study, we demonstrated direct neuroprotective effect of RA using H2O2-induced oxidative challenge in N2A mouse neuroblastoma cells. The mechanism of neutralization of H2O2-induced toxicity by RA was evaluated using MTT, lactate dehydrogenase, mitochondrial membrane potential (MMP), intracellular ROS, and comet assays. Up-regulation of brain neuronal markers at molecular level was performed by RT-PCR. KEY FINDINGS: Results presented in the paper indicate that H2O2-induced cytotoxicity in N2A cells was suppressed by treatment with RA. Moreover, RA is very effective in attenuating the disruption of lactate dehydrogenase, mitochondrial membrane potential and intracellular ROS. Pretreatment with RA significantly prevents genotoxicity (3.7-fold, p<0.01) and promotes the up-regulation of tyrosine hydroxylase (TH) (4.5-fold, p<0.01), and brain-derived neurotrophic factor (BDNF) genes (5.4-fold, p<0.01) against H2O2-induced cytotoxicity in N2A cells. SIGNIFICANCE: Our results revealed that N2A cells are suitable cellular models to evaluate neuroprotective effects of RA, and suggest that RA may potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Ghaffari, Hadi AU - Ghaffari H AD - Department of Studies in Biotechnology, University of Mysore, Mysore, Karnataka, India. FAU - Venkataramana, M AU - Venkataramana M AD - DRDO-BU-Centre for Life Sciences, Bharathiar University Campus, Coimbatore, Tamil Nadu 640046, India. FAU - Jalali Ghassam, Behrouz AU - Jalali Ghassam B AD - Department of Studies in Biotechnology, University of Mysore, Mysore, Karnataka, India. FAU - Chandra Nayaka, S AU - Chandra Nayaka S AD - Department of Studies in Biotechnology, University of Mysore, Mysore, Karnataka, India. FAU - Nataraju, A AU - Nataraju A AD - Department of Biochemistry, Karnataka State Open University (KSOU), Mysore-06, India. FAU - Geetha, N P AU - Geetha NP AD - Department of Studies in Biotechnology, University of Mysore, Mysore, Karnataka, India. FAU - Prakash, H S AU - Prakash HS AD - Department of Studies in Biotechnology, University of Mysore, Mysore, Karnataka, India. Electronic address: hsp@appbot.uni-mysore.ac.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140721 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cinnamates) RN - 0 (Depsides) RN - 0 (Neuroprotective Agents) RN - 0 (Reactive Oxygen Species) RN - 0 (Tetrazolium Salts) RN - 0 (Thiazoles) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EUY85H477I (thiazolyl blue) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Brain/drug effects MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Line, Tumor MH - Cinnamates/*pharmacology MH - Comet Assay MH - Depsides/*pharmacology MH - Hydrogen Peroxide/*chemistry MH - Membrane Potential, Mitochondrial/drug effects MH - Mice MH - Neurons/*drug effects/metabolism MH - Neuroprotective Agents/*pharmacology MH - Oxidative Stress MH - Reactive Oxygen Species/metabolism MH - Tetrazolium Salts MH - Thiazoles MH - Tyrosine 3-Monooxygenase/metabolism MH - Rosmarinic Acid OTO - NOTNLM OT - DNA damage OT - Gene expression OT - N2A cells OT - Neuroprotection OT - Oxidative stress OT - Rosmarinic acid EDAT- 2014/07/25 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/07/25 06:00 PHST- 2014/01/25 00:00 [received] PHST- 2014/06/10 00:00 [revised] PHST- 2014/07/10 00:00 [accepted] PHST- 2014/07/25 06:00 [entrez] PHST- 2014/07/25 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0024-3205(14)00619-5 [pii] AID - 10.1016/j.lfs.2014.07.010 [doi] PST - ppublish SO - Life Sci. 2014 Sep 15;113(1-2):7-13. doi: 10.1016/j.lfs.2014.07.010. Epub 2014 Jul 21.