Protective Effect of Xiao-Xu-Ming Decoction-Mediated Inhibition of ROS/NLRP3 Axis on Lipopolysaccharide-Induced Acute Lung Injury In Vitro and In Vivo.

Yijin Xiang,Xuxia Bao,Min Cai,Dingfang Cai,Xiangting Li,Yi Rong Li

doi:10.1155/2021/8257495

Abstract

Background As a traditional Chinese medicine prescription, Xiao-Xu-Ming decoction (XXMD) could reduce the incidence of lung infection of patients with cerebral infarction. Nonetheless, the therapeutic mechanisms of XXMD in acute lung injury (ALI) remain to be elucidated. Our study was aimed to assess the effects of XXMD protects against ALI. Methods ALI model was induced by intraperitoneal injection of lipopolysaccharide (LPS) in vivo. In vitro, human pulmonary alveolar epithelial cells (HPAEpiC) were treated with XXMD and were followed by LPS treatment. The levels of ZO-1, CLDN4, NLRP3, and caspase 1 were detected by Western blot, and the content of IL-1 and IL-18 was determined by ELISA. Transepithelial electrical resistance was used to detect the cell permeability. The reactive oxygen species (ROS) levels within the cells were evaluated by flow cytometry. Results Our results showed that XXMD attenuated LPS-induced oxidative stress, barrier dysfunction, and the activation of NLRP3 inflammasome in vitro, as evidenced by enhanced ROS production, TEER levels, expression of NLRP3 and caspase 1 (p20) and release of IL-1β and IL-18, and weakened cell permeability. In addition, XXMD could counteract the effects of NLRP3 overexpression on HPAEpiC and vice versa. XXMD treatment also ameliorated the degree of neutrophil infiltration, barrier dysfunction, and the activation of NLRP3 in LPS-induced ALI lung tissues in vivo. Conclusion The findings showed that XXMD could alleviate LPS-induced ALI injury and inhibit inflammation and suppress ROS/NLRP3 signaling pathway, which were involved in these protective effects.

Highlights

As a traditional Chinese medicine prescription, Xiao-Xu-Ming decoction (XXMD) could reduce the incidence of lung infection of patients with cerebral infarction
It was reported that excessive reactive oxygen species (ROS) could activate NLRP3 inflammasome and lead to the activation of caspase 1 and the release of IL-1β and IL-18. e results of Western blot and enzyme-linked immunosorbent assay (ELISA) showed that LPS treatment could significantly increase the levels of NLRP3, caspase 1 (p20), IL-1β, and IL-18 as compared with the control group; these levels were markedly reversed by XXMD treatment as compared with LPS group (Figures 1(c) and 1(d))
Our results demonstrated that XXMD could reduce increase transepithelial electrical resistance (TEER) level and decrease cell permeability, the activation of NLRP3, and the level of IL-1β and IL-18 as compared with LPS group, which was reversed by NLRP3 overexpression (P < 0.001) (Figures 3(a)–3(e)). ese findings confirmed that XXMD inhibits barrier dysfunction and the activation of NLRP3 induced by LPS

Summary

Introduction

As a traditional Chinese medicine prescription, Xiao-Xu-Ming decoction (XXMD) could reduce the incidence of lung infection of patients with cerebral infarction. Our results showed that XXMD attenuated LPS-induced oxidative stress, barrier dysfunction, and the activation of NLRP3 inflammasome in vitro, as evidenced by enhanced ROS production, TEER levels, expression of NLRP3 and caspase 1 (p20) and release of IL-1β and IL-18, and weakened cell permeability. XXMD treatment ameliorated the degree of neutrophil infiltration, barrier dysfunction, and the activation of NLRP3 in LPS-induced ALI lung tissues in vivo. E findings showed that XXMD could alleviate LPS-induced ALI injury and inhibit inflammation and suppress ROS/NLRP3 signaling pathway, which were involved in these protective effects. Endogenous and exogenous injury factors performed a role in the lungs, and they may cause lung cells to be exposed to excessive amounts of reactive oxygen species (ROS), inflammatory cell infiltration, and proinflammatory mediator production, which were involved in the process of ALI [4]. In recent years, supportive techniques of treating ALI have improved to a great extent, but, so far, there is no effective treatment. erefore, exploring an effective treatment strategy for ALI has become a hot spot in clinical research

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