Naoxintong/PPARα Signaling Inhibits H9c2 Cell Apoptosis and Autophagy in Response to Oxidative Stress.

Huimin Xu,Buchang Zhao,Yongzhong Hou,Chunxiao Li,Jianhua Jin,Lu Chen,Juanjuan Shi,Hong Wang,Qinggang Xu

doi:10.1155/2016/4370381

Abstract

Naoxintong (NXT) is an empirical formula based on the principle of traditional Chinese medicine, which has been approved by China Food and Drug Administration (CFDA) and is widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. The aim of this study is to investigate the protective mechanism of NXT on H9c2 cells (cardiogenic cell line) in response to H2O2. MTT, Western blot, and flow cytometry (FCM) methods were used to identify the protective effect of NXT extract on H2O2-induced H9c2 cells. Here we found that NXT extract significantly increased H9c2 cell viability and reduced H2O2-induced cell apoptosis and autophagy. More importantly, NXT inhibited H2O2-induced H9c2 cell apoptosis and autophagy by increasing PPARα protein levels. In contrast, silenced PPARα terminated NXT protective effect on H2O2-induced H9c2 cells. These findings suggest that NXT/PPARα signaling suppressed H2O2-induced H9c2 cell apoptosis and autophagy.

Highlights

Naoxintong (NXT) is an empirical formula based on the principle of traditional Chinese medicine, which has been approved by China Food and Drug Administration (CFDA, Z20025001) and widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China
Our results show that NXT extract reversed this apoptotic signaling by inhibiting caspase-3 activation (Figure 2(c)); subsequently, cleaved PARP-1 was decreased in H9c2 cells treated with NXT extract (Figure 2(d)). These findings suggest that NXT inhibited the H9c2 cell apoptosis through inhibiting activation of caspase-3/PARP-1 signaling pathway
The results show that H2O2 significantly induced cell apoptosis, but NXT reversed this event (Figure 3), suggesting that NXT extract inhibited H2O2-induced H9c2 cell apoptosis associated with increased antiapoptotic protein levels

Summary

Introduction

Naoxintong (NXT) is an empirical formula based on the principle of traditional Chinese medicine, which has been approved by China Food and Drug Administration (CFDA, Z20025001) and widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. NXT reduces the development of diabetic retinopathy [4] and cardiomyocyte damage in response to Evidence-Based Complementary and Alternative Medicine reactive oxygen species (ROS) [5]; the mechanism of NXT on the cardiomyocyte apoptosis and autophagy in response to oxidative stress is still unclear. Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. ROS is a main oxidative stress in cardiovascular damage. ROS is a byproduct of the normal metabolism of oxygen and has important roles in the cell signaling and homeostasis. Our previous study shows that the extract of Angelica sinensis and Ligusticum chuanxiong has protective effect against H2O2-induced endothelial cell damage [9] and inhibits rat vascular smooth muscle cell proliferation [10]. We found that NXT activated PPARα signaling decreased H2O2-induced H9c2 cell apoptosis and autophagy

Materials and Methods

Results

Figure Results

Discussions