Potent effects of flavonoid-rich extract from Rosa laevigata Michx fruit against hydrogen peroxide-induced damage in PC12 cells via attenuation of oxidative stress, inflammation and apoptosis.

Min Liu,Jinyong Peng,Yanyan Zhao,Xu Han,Chen Liang,Lianhong Yin,Yan Qi,Changkai Sun,Youwei Xu,Lina Xu

doi:10.3390/molecules190811816

Min Liu, Jinyong Peng + Show 8 more

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https://doi.org/10.3390/molecules190811816

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Journal: Molecules (Basel, Switzerland)	Publication Date: Aug 7, 2014
Citations: 78	License type: CC BY 4.0

Affiliation: Dalian Medical University

Abstract

Oxidative stress-induced neuronal death has an important role in the pathogenesis of neurodegenerative disorders. The effects and mechanisms of action of the total flavonoids (TFs) from Rosa laevigata Michx fruit against hydrogen peroxide (H2O2)-induced oxidative injury in PC12 cells were investigated in this study. The results demonstrated that the TFs protected against cell apoptosis, DNA and mitochondrial damage caused by H2O2 based on single cell gel electrophoresis, in situ terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL), flow cytometry and transmission electron microscope (TEM) assays. In addition, the TFs notably decreased cytochrome C release from mitochondria into the cytosol and intracellular Ca2+ levels, and diminished intracellular generation of reactive oxygen species (ROS). Furthermore, the TFs inhibited the phosphorylation levels of JNK, ERK and p38 MAPK as well as down-regulated the expressions of IL-1, IL-6, TNF-α, Fas, FasL, CYP2E1, Bak, caspase-3, caspase-9, p53, COX-2, NF-κB, AP-1, and up-regulated the expressions of Bcl-2 and Bcl-xl. In conclusion, these results suggest that the TFs from R. laevigata Michx fruit show good effects against H2O2-induced oxidative injury in PC12 cells by adjusting oxidative stress, and suppression of apoptosis and inflammation, and could be developed as a potential candidate to prevent oxidative stress in the future.

Highlights

Oxidative injury has been involved in the pathogenesis of some neurological diseases includingParkinson's disease, Alzheimer’s disease [1] and stroke [2]
The effects of total flavonoids (TFs) and H2O2 on cell viability were investigated first, and we found that the TFs in the
Obvious morphological changes were found in different groups using bright field images, Acridine orange (AO)/ethidium bromide (EB) and DAPI staining of PC12 cells

Summary

Introduction

Oxidative injury has been involved in the pathogenesis of some neurological diseases includingParkinson's disease, Alzheimer’s disease [1] and stroke [2]. Oxidative stress can enhance intracellular Ca2+ concentration [4], and activate neuro-inflammatory reactions [5] and apoptotic pathways. When these processes happen, different types of cells can generate lots of hydrogen peroxide (H2O2). Mitogen-activated protein kinases (MAPKs) can regulate complicated signaling pathways related to cell growth and apoptosis [8]. These kinases can change cellular signaling in the nucleus by activation of oxidation sensitive transcription factors, including activator protein-1 (AP-1) and nuclear factor-κappaB (NF-κB) [9]. Therapeutic strategies aimed at blocking of reactive oxygen species (ROS)-induced apoptosis might be effective for the treatment of these diseases

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Conclusion