Gypenosides Inhibit Inflammatory Response and Apoptosis of Endothelial and Epithelial Cells in LPS-Induced ALI: A Study Based on Bioinformatic Analysis and in vivo/vitro Experiments

Abstract

Introduction: Severe inflammatory response leads to poor prognosis of acute lung injury (ALI), the role of gypenosides (GPs) on ALI is not fully clear. The study aimed at investigating the effects of GPs on ALI. Methods: We firstly established LPS-induced ALI mice model. Then, we tested whether GPs contributed to alleviate inflammatory response and lung injury of ALI in vivo. In order to identify specific mechanisms of the phenomenon, we conducted a bioinformatic analysis of LPS-induced ALI mice based on GEO database to identify hub differentially expressed genes (DEGs). PPI network of the DEGs was used to find hub-genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted based on the DAVID database to identify which pathways the genes enriched. Then, we tested whether GPs inhibited lung injury and inflammatory response via the enriched pathways. We also tested whether GPs inhibited the apoptosis of endothelial and epithelial cells secondary to severe inflammation. Results: We found GPs significantly alleviated lung injury and improved the survival rate of LPS-induced ALI mice in vivo. Bioinformatic analysis identified 20 hub-genes from DEGs, they were mainly enriched in NF-κB and TNF-α pathways. GPs could reduce the lung injury and inflammatory response via inhibiting NF-κB and TNF-α pathways in vivo. Our results indicated that GPs also inhibited inflammatory response of epithelial and endothelial cells via NF-κB and TNF-α pathways in vitro. Severe inflammatory response could also lead to apoptosis of endothelial and epithelial cells. Our results indicated that GPs effectively inhibited the apoptosis of endothelial and epithelial cells. Conclusion:Our study suggested GPs contributed to alleviated lung injury in vivo and inhibited inflammation and apoptosis of endothelial and epithelial cells in vitro, providing novel strategies for the prevention and therapy for ALI.

Oxypaeoniflorin Prevents Acute Lung Injury Induced by Lipopolysaccharide through the PTEN/AKT Pathway in a Sirt1‐Dependent Manner

“…LPS challenge also gives rise to apoptosis of pulmonary epithelial cells, the inhibition of which is important for maintaining pulmonary function [ 17 ]. Herein, we detected the makers of apoptosis in LPS-treated lung tissues.…”

M2 Macrophage-Derived Exosomes Inhibit Apoptosis of HUVEC Cell through Regulating miR-221-3p Expression

“…HUVEC dysfunction and morphological damage can manifest as multiple physiological effects, including adhesion of leukocytes, vasoconstriction, platelet activation, oxidative stress, and inflammation, which ultimately lead to the development of AS. Therefore, promoting HUVEC proliferation, inhibiting HUVEC apoptosis, and suppressing HUVEC inflammation have become key strategies for the prevention and control of AS [ 9 , 16 ]. Undoubtedly, macrophages are the primary concern in the treatment of HUVEC cell injury.…”

Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways

“…In recent years, an increasing number of studies have demonstrated that the development of ALI is related to inflammation, oxidative stress, apoptosis, and cellular immunity. [16][17][18][19] However, mortality due to ALI continues to be high. There are many published reports on the activity of natural products to treat ALI.…”