Oncotarget

Research Papers:

Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling pathway

Dandan Han, Wei Chen, Xiaolong Gu, Ruixue Shan, Jiaqi Zou, Gang Liu, Muhammad Shahid, Jian Gao and Bo Han _

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Oncotarget. 2017; 8:14680-14692. https://doi.org/10.18632/oncotarget.14747

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Abstract

Dandan Han1,*, Wei Chen1,*, Xiaolong Gu1, Ruixue Shan1, Jiaqi Zou1, Gang Liu1, Muhammad Shahid1, Jian Gao1, Bo Han1

1College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China

*These authors have contributed equally to this work

Correspondence to:

Bo Han, email: hanbo@cau.edu.cn

Keywords: chlorogenic acid, MC3T3-E1 cells, oxidative stress, Nrf2/HO-1 pathway, cytoprotection

Received: November 22, 2016     Accepted: January 11, 2017     Published: January 19, 2017

ABSTRACT

Osteoporosis is a disorder of bone and its development is closely associated with oxidative stress and reactive oxygen species (ROS). Chlorogenic acid (CGA) has potential antioxidant effects and its pharmacological action in osteoblasts is not clearly understood. The present study aimed to clarify the protective effects and mechanisms of CGA on hydrogen peroxide (H2O2)-induced oxidative stress in osteoblast cells. MC3T3-E1 cells were treated with H2O2 to induce oxidative stress model in vitro. Cells were treated with CGA prior to H2O2 exposure, the intracellular ROS production, malondialdehyde content, nitric oxide release and glutathione level were measured. We also investigated the protein levels of heme oxygenase-1 (HO-1), the nuclear translocation of transcription factor NF-erythroid 2-related factor (Nrf2) and the phosphorylation levels of Akt in CGA-treated cells. The results showed that pretreatment of CGA could reverse the inhibition of cell viability and suppress the induced apoptosis and caspase-3 activity. Additionally, it significantly reduced H2O2-induced oxidative damage in a dose-dependent manner. Furthermore, it induced the protein expression of HO-1 together with its upstream mediator Nrf2, and activated the phosphorylation of Akt in MC3T3-E1 cells. LY294002, a PI3K/Akt inhibitor, significantly suppressed the CGA-induced Nrf2 nuclear translocation and HO-1 expression. Reduction of cell death mediated by CGA in presence of H2O2 was significantly inhibited by Zinc protoporphyrin IX (a HO-1 inhibitor) and LY294002. These data demonstrated that CGA protected MC3T3-E1 cells against oxidative damage via PI3K/Akt-mediated activation of Nrf2/HO-1 pathway, which may be an effective drug in treatment of osteoporosis.


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