Apigenin-7-glycoside prevents LPS-induced acute lung injury via downregulation of oxidative enzyme expression and protein activation through inhibition of MAPK phosphorylation.

Kun-Cheng Li,Wen-Tsong Hsieh,Shyh-Shyun Huang,Guan-Jhong Huang,Yu-Ling Ho,Yuan-Shiun Chang

doi:10.3390/ijms16011736

Abstract

Apigenin-7-glycoside (AP7Glu) with multiple biological activities is a flavonoid that is currently prescribed to treat inflammatory diseases such as upper respiratory infections. Recently, several studies have shown that its anti-inflammatory activities have been strongly linked to the inhibition of secretion of pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOs) and cyclooxygenase-2 (COX-2) induced through phosphorylation nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) pathways. Additionally, inflammation, which can decrease the activities of antioxidative enzymes (AOEs) is also observed in these studies. At the same time, flavonoids are reported to promote the activities of heme oxygenase-1 (HO-1) decreased by LPS. The purpose of this study was to assess these theories in a series of experiments on the suppressive effects of AP7Glu based on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and acute lung injury in mice in vivo. After six hours of lipopolysaccharide (LPS) stimulation, pulmonary pathological, myeloperoxidase (MPO) activity, total polymorphonuclear leukocytes (PMN) cells, cytokines in bronchoalveolar lavage fluid (BALF) and AOEs, are all affected and changed. Meanwhile, our data revealed that AP7Glu not only did significantly inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti-inflammatory effect through the MAPK and inhibitor NF-κB (IκB) pathways.

Highlights

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases induced by many extreme conditions including severe sepsis, severe bacterial pneumonia, trauma and burn
This study examined whether inhibitor NF-κB (IκB), ERK/mitogen-activated protein kinases (MAPK), p38/MAPK and JNK/MAPK pathways and oxidative enzymes (AOEs and heme oxygenase-1 (HO-1)) were involved in the mechanisms to underlie the beneficial effects
In order to investigate whether the inhibition of NO production was due to decreased inducible nitric oxide synthase (iNOs) and COX-2 protein level, the effect of AP7Glu on iNOs and COX-2 protein expression was studied by immunoblot

Summary

Introduction

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases induced by many extreme conditions including severe sepsis, severe bacterial pneumonia, trauma and burn. The main symptoms of ALI are alveolar edema and uncontrolled neutrophil migrate to the lung [1]. The identification of new molecules that can modulate ALI-associated inflammation is an expected and significant goal of pharmaceutical companies [2]. The fairly uncontrolled pathophysiological mechanisms of ARDS and ALI results in oxidative damage to functional macromolecules such as proteins and lipids, that leads to increasing the thickness of the alveolar wall and pulmonary inflammation. Those symptoms will cause many further disorders, like inflammation, cancer, atherosclerosis, neurodegeneration and aging-related diseases [3]

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