Isoliquiritigenin Inhibits Cigarette Smoke-Induced COPD by Attenuating Inflammation and Oxidative Stress via the Regulation of the Nrf2 and NF-κB Signaling Pathways.

Duo Yu,Tiejun Wang,Xueshibojie Liu,Zhihui Ming,Guangxin Zhang

doi:10.3389/fphar.2018.01001

Abstract

Chronic obstructive pulmonary disease (COPD) is the major leading cause of disease with high-mortality worldwide. Cigarette smoke (CS) is a major factor for COPD. CS causes chronic inflammation and oxidative stress, which contributes to lung dysfunction in COPD. Isoliquiritigenin (ILG), a natural flavonoid derived from the root of liquorice, has been reported to possess antiinflammatory and antioxidant activity. In the present study, we tested the mechanism and protective effects of ILG on CS-induced COPD. Mice were exposed to CS for 2 h twice a day for 4 weeks. ILG was given orally 1 h before CS exposure twice a day for 4 weeks. The bronchial alveolar lavage fluid was collected to test the levels of inflammatory cytokines and the number of inflammatory cells. The lung tissues were obtained to evaluate the pathological changes, lung edema, myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, as well as the expression of the nuclear factor-erythroid 2 (Nrf2) and nuclear factor κB (NF-κB) signaling pathways. The results showed that ILG reduced the infiltration of inflammatory cells and the production of inflammatory cytokines. ILG also reversed CS-induced lung pathological injuries, wet/dry ratio, MPO activity, and MDA level. Further research also showed that ILG dose-dependently up-regulated the expression of Nrf2 and down-regulated the expression of NF-κB signaling pathways induced by CS. In conclusion, ILG protected against CS-induced COPD by inhibiting inflammatory and oxidative stress via the regulation of the Nrf2 and NF-κB signaling pathways.

Highlights

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease that is characterized by persistent respiratory symptoms due to small airway wall fibrosis, thickening, hypersecretion of mucus, oxidative stress, and inflammation in the lung (Zheng et al, 2008; Eapen et al, 2017; Vogelmeier et al, 2017a)
The results showed that lung wet/dry ratio was obviously increased after Cigarette smoke (CS) exposure
The results showed that the levels of TNF-α and IL-1β in the Bronchial alveolar lavage fluid (BALF) were significantly increased in the CS group compared with those in the control group

Summary

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease that is characterized by persistent respiratory symptoms due to small airway wall fibrosis, thickening, hypersecretion of mucus, oxidative stress, and inflammation in the lung (Zheng et al, 2008; Eapen et al, 2017; Vogelmeier et al, 2017a). Studies have demonstrated that ILG inhibits early brain impairments by regulating nuclear factor κB (NF-κB) and NLRP3 inflammasome pathways via triggering nuclear factor-erythroid 2 (Nrf2) activity (Zeng et al, 2017) This inhibition of the NF-κB and NLRP3 inflammasome is an anti-inflammatory mechanism common to other flavonoids (Li et al, 2016; Menghini et al, 2016). ILG has previously been shown to inhibit adipose tissue inflammation by inhibiting both NLRP3 inflammasomedependent and independent mechanisms and reducing the adipose tissue fibrosis by regulating sensors of innate immunity (Watanabe et al, 2016). It remains unclear whether ILG is effective for treating COPD. The mechanism and protective effect of ILG on CS-induced COPD were tested in the present study

MATERIALS AND METHODS

RESULTS

DISCUSSION

CONCLUSION