Corylin Ameliorates LPS-Induced Acute Lung Injury via Suppressing the MAPKs and IL-6/STAT3 Signaling Pathways

I-Chen Chen,Yu-Hsin Tseng,Tzu-Chieh Lin,Hsin-Han Tseng,Jong-Hau Hsu,Zen-Kong Dai,Po-Len Liu,Chia-Yang Li,Shu-Chi Wang,Yi-Ting Chen,Yuan-Ru Chen,Jau-Ling Suen,Hsin-En Wu

doi:10.3390/ph14101046

Abstract

Acute lung injury (ALI) is a high mortality disease with acute inflammation. Corylin is a compound isolated from the whole plant of Psoralea corylifolia L. and has been reported to have anti-inflammatory activities. Herein, we investigated the therapeutic potential of corylin on lipopolysaccharides (LPS)-induced ALI, both in vitro and in vivo. The levels of proinflammatory cytokine secretions were analyzed by ELISA; the expressions of inflammation-associated proteins were detected using Western blot; and the number of immune cell infiltrations in the bronchial alveolar lavage fluid (BALF) were detected by multicolor flow cytometry and lung tissues by hematoxylin and eosin (HE) staining, respectively. Experimental results indicated that corylin attenuated LPS-induced IL-6 production in human bronchial epithelial cells (HBEC3-KT cells). In intratracheal LPS-induced ALI mice, corylin attenuated tissue damage, suppressed inflammatory cell infiltration, and decreased IL-6 and TNF-α secretions in the BALF and serum. Moreover, it further inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including p-JNK, p-ERK, p-p38, and repressed the activation of signal transducer and activator of transcription 3 (STAT3) in lungs. Collectively, our results are the first to demonstrate the anti-inflammatory effects of corylin on LPS-induced ALI and suggest corylin has significant potential as a novel therapeutic agent for ALI.

Highlights

We hypothesized that corylin might have protective effects on LPS-induced Acute lung injury (ALI); in this study, we aimed to examine the anti-inflammatory effects of corylin on LPS-induced ALI both in vitro and in vivo
The effects of corylin on IL-6 production by LPS-induced HBEC3-KT cells was examined, and experimental results showed that corylin significantly suppressed the production of IL-6 by LPS-induced HBEC3-KT
Since the number of inflammatory cell infiltrations is a hallmark of ALI, we explored whether corylin treatment could suppress LPS-induced lung inflammation

Summary

Introduction

The hallmark of ALI/ARDS is that injury to the epithelium results in the release of inflammatory mediators, promoting the initial influx of neutrophils and macrophages into the sites of injury, following an increase in cytokine production and flooding of protein-rich fluid into the alveolar space [3,6]. It has been shown that IL-6 plays an essential role in phosphorylation of signal transducer and activator of transcription 3 (STAT3), resulting in enhancing neutrophil recruitment and decreasing bacterial burdens [8,9,10]. Other signal transduction pathways that participate in mediating lung inflammation include JAK/STAT, NF-κB, and mitogen-activated protein kinase (MAPK) signal transduction [10,11,12,13]

Objectives

Methods

Results

Discussion

Conclusion