PNS-R1 inhibits Dex-induced bronchial epithelial cells apoptosis in asthma through mitochondrial apoptotic pathway

Wenjing Zou,Chao Niu,Zhou Fu,Caihui Gong

doi:10.1186/s13578-019-0279-x

Abstract

Dexamethasone (Dex) are widely used for the treatment of asthma. However, they may cause apoptosis of bronchial epithelial cells and delay the recovery of asthma. Therefore, it is an urgent problem to find effective drugs to reduce this side effects. Panax notoginseng saponins R1 (PNS-R1) is known to exhibit anti-oxidative and anti-apoptotic properties in many diseases. We aim to investigate whether PNS-R1 can reduce Dex-induced apoptosis in bronchial epithelial cells. In this study, the anti-apoptotic effects of PNS-R1 were investigated by conducting in vitro and in vivo. Annexin V-FITC/PI staining flow cytometry analysis and TUNEL assay were conducted to detect apoptotic cells. Mitochondrial membrane potential was detected by JC-1 analysis. Western blotting and immunohistochemical analysis were conducted to measure caspase3, Bcl-2, Bax, Cyt-c, Apaf-1, cleaved-caspase3 and cleaved-caspase9 levels in lung tissues and 16HBE cells. Our findings demonstrated that Dex could induce apoptosis of bronchial epithelial cells and upregulate caspase3 expression of lung tissues. Western blot showed that Dex increased Bax, Cyt-c, Apaf-1, cleaved-caspase9, cleaved-caspase3 expression and decreased Bcl-2 expression. PNS-R1 could suppress Dex-induced apoptosis of bronchial epithelial cells by inhibiting Bax, Cyt-c, Apaf-1, cleaved-caspase9, cleaved-caspase3 expression and upregulating Bcl-2 expression. Flow cytometry analysis showed PNS-R1 alleviated JC-1 positive cells induced by Dex in 16HBE cells. These results showed that PNS-R1 alleviated Dex-induced apoptosis in bronchial epithelial cells by inhibition of mitochondrial apoptosis pathway. Furthermore, our findings highlighted the potential use of PNS-R1 as an adjuvant drug to treat asthma.

Highlights

Asthma is one of the most common chronic diseases worldwide-an increasing tendency of the incidence [1]
In our previous study [16, 17], we showed that Dex inhibited bronchial epithelial cell proliferation and migration in a dose- and time-dependent manner
PNS‐R1 protected against Dex‐induced apoptosis in 16HBE by inhibiting the mitochondrial apoptosis pathway We have shown that Panax notoginseng saponins R1 (PNS-R1) could influence mitochondrial apoptosis pathway in asthmatic mice treated with Dex

Summary

Introduction

Asthma is one of the most common chronic diseases worldwide-an increasing tendency of the incidence [1]. Inhaled corticosteroids (ICS) are the most commonly used drugs for the treatment of asthma [2]. Dex therapy in asthma can induce airway epithelial cell apoptosis and inhibit cell proliferation, which in turn inhibit epithelial repair and lead to airway remodeling [3]. Some studies suggested that the use of inhaled corticosteroids could affect airway remodeling and epithelial. Panax notoginseng saponins R1 (PNS-R1), which is an important component of the Chinese medicine Sanqi, is known for its anti-inflammatory, anti-oxidative and anti-apoptotic properties [5]. Previous studies have demonstrated that PNS-R1 exerted protective effects against ischemia-induced apoptosis in vitro and in vivo models of cardiomyocytes [6]. PNS-R1 has been shown to promote angiogenesis in human umbilical vein endothelial cells [7]. PNS-R1 could inhibit PC12 cell apoptosis induced by oxidative injury [8].

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