Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation

Objectives. To investigate the protective effect of ginsenoside Rg1 on relieving sepsis-induced lung inflammation and injury in vivo and in vitro. Methods. Cultured human pulmonary epithelial cell line A549 was challenged with LPS to induce cell injury, and CLP mouse model was generated to mimic cli...

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Main Authors: Qian-Lu Wang, Lei Yang, Yue Peng, Min Gao, Ming-Shi Yang, Wei Xing, Xian-Zhong Xiao
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/6453296
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author Qian-Lu Wang
Lei Yang
Yue Peng
Min Gao
Ming-Shi Yang
Wei Xing
Xian-Zhong Xiao
author_facet Qian-Lu Wang
Lei Yang
Yue Peng
Min Gao
Ming-Shi Yang
Wei Xing
Xian-Zhong Xiao
author_sort Qian-Lu Wang
collection DOAJ
description Objectives. To investigate the protective effect of ginsenoside Rg1 on relieving sepsis-induced lung inflammation and injury in vivo and in vitro. Methods. Cultured human pulmonary epithelial cell line A549 was challenged with LPS to induce cell injury, and CLP mouse model was generated to mimic clinical condition of systemic sepsis. Rg1 was applied to cells or animals at indicated dosage. Apoptosis of cultured cells was quantified by flow cytometry, along with ELISA for inflammatory cytokines in supernatant. For septic mice, lung tissue pathology was examined, plus ELISA assay for serum cytokines. Western blotting was used to examine the activation of inflammatory pathways and ER stress marker proteins in both cells and mouse lung tissues. Reactive oxygen species (ROS) level was quantified by DCFDA kit. Results. Ginsenoside Rg1 treatment remarkably suppressed apoptosis rate of LPS-induced A549 cells, relieved mouse lung tissue damage, and elevated survival rate. Rg1 treatment also rescued cells from LPS-induced intracellular ROS. In both A549 cells and mouse lung tissues, further study showed that Rg1 perfusion significantly suppressed the secretion of inflammatory cytokines including tumor necrosis factor- (TNF-) alpha and interleukin- (IL-) 6 and relieved cells from ER stress as supported by decreased expression of marker proteins via upregulating sirtuin 1 (SIRT1). Conclusion. Our results showed that ginsenoside Rg1 treatment effectively relieved sepsis-induced lung injury in vitro and in vivo, mainly via upregulating SIRT1 to relieve ER stress and inflammation. These findings provide new insights for unrevealing potential candidate for severe sepsis accompanied with lung injury.
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spelling doaj-art-32fdf7b6354c41e3862c2dba8ed6fa042025-02-03T06:44:17ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/64532966453296Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and InflammationQian-Lu Wang0Lei Yang1Yue Peng2Min Gao3Ming-Shi Yang4Wei Xing5Xian-Zhong Xiao6Department of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, ChinaDepartment of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha 410003, ChinaDepartment of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, ChinaDepartment of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, ChinaDepartment of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, ChinaDepartment of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, ChinaDepartment of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410078, ChinaObjectives. To investigate the protective effect of ginsenoside Rg1 on relieving sepsis-induced lung inflammation and injury in vivo and in vitro. Methods. Cultured human pulmonary epithelial cell line A549 was challenged with LPS to induce cell injury, and CLP mouse model was generated to mimic clinical condition of systemic sepsis. Rg1 was applied to cells or animals at indicated dosage. Apoptosis of cultured cells was quantified by flow cytometry, along with ELISA for inflammatory cytokines in supernatant. For septic mice, lung tissue pathology was examined, plus ELISA assay for serum cytokines. Western blotting was used to examine the activation of inflammatory pathways and ER stress marker proteins in both cells and mouse lung tissues. Reactive oxygen species (ROS) level was quantified by DCFDA kit. Results. Ginsenoside Rg1 treatment remarkably suppressed apoptosis rate of LPS-induced A549 cells, relieved mouse lung tissue damage, and elevated survival rate. Rg1 treatment also rescued cells from LPS-induced intracellular ROS. In both A549 cells and mouse lung tissues, further study showed that Rg1 perfusion significantly suppressed the secretion of inflammatory cytokines including tumor necrosis factor- (TNF-) alpha and interleukin- (IL-) 6 and relieved cells from ER stress as supported by decreased expression of marker proteins via upregulating sirtuin 1 (SIRT1). Conclusion. Our results showed that ginsenoside Rg1 treatment effectively relieved sepsis-induced lung injury in vitro and in vivo, mainly via upregulating SIRT1 to relieve ER stress and inflammation. These findings provide new insights for unrevealing potential candidate for severe sepsis accompanied with lung injury.http://dx.doi.org/10.1155/2019/6453296
spellingShingle Qian-Lu Wang
Lei Yang
Yue Peng
Min Gao
Ming-Shi Yang
Wei Xing
Xian-Zhong Xiao
Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation
Mediators of Inflammation
title Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation
title_full Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation
title_fullStr Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation
title_full_unstemmed Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation
title_short Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation
title_sort ginsenoside rg1 regulates sirt1 to ameliorate sepsis induced lung inflammation and injury via inhibiting endoplasmic reticulum stress and inflammation
url http://dx.doi.org/10.1155/2019/6453296
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