Integrated Network Pharmacology and Lipidomics to Reveal the Inhibitory Effect of Qingfei Oral Liquid on Excessive Autophagy in RSV-Induced Lung Inflammation

Abstract

Background: Respiratory syncytial virus (RSV) can cause varying degrees of lung inflammation in children. Qingfei Oral Liquid (QF) is effective in treating childhood RSV-induced lung inflammation (RSV-LI) in clinics, but its pharmacological profiles and mechanisms remain unclear.Methods: This study combined network Pharmacology, lipidomics, pharmacodynamics, and pathway validation to evaluate the therapeutic mechanisms of QF. Using Cytoscape (v3.8.2) and enrichment analyses from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), a global view of the putative compound-target-pathway network was created. The corresponding lipidomic profiles were then used to detect differently activated lipids, revealing the metabolic pathway, using ultra-high-performance liquid chromatography linked to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Meanwhile, the in vivo efficiency of QF, the enrichment pathway, and the excessive autophagy inhibition mechanisms were validated in RSV-infected mice models.Results: The network pharmacology results demonstrated 117 active compounds acted directly upon 101 core targets of QF against RSV-LI. The most significantly enriched pathway was the PI3K/Akt/mTOR signaling pathway (p < 0.05). In addition, untargeted lipidomics were performed, and it was revealed that higher lung levels of DAG 30:0, DAG 30:5, DAG 32:0, DAG 16:0_18:0, DAG 17:0_17:0, DAG 34:1, DAG 36:0, DAG 36:1 in the RSV-LI group were decreased after QF administration (FDR < 0.05, FC > 1.2). Lipin-1, a key enzyme in DAG synthesis, was increased in the RSV-LI mouse model. Animal experiments further validated that QF inhibited the PI3K/Akt/mTOR signaling pathway, with lower lung levels of phosphorylated PI3K, AKT and mTOR, as well as its related proteins of lipin-1 and VPS34 (p < 0.01). Finally, pharmacodynamic investigations indicated that QF reduced airway inflammation caused by excessive autophagy by decreasing lung levels of RSV F and G proteins, Beclin-1, Atg5, and LC3B II, IL-1 and TNF-α (p < 0.05).Conclusion: Lipidomic-based network pharmacology, along with experimental validation, may be effective approaches for illustrating the therapeutic mechanism of QF in the treatment of RSV-LI.

Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism

“…The pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, are vital for the onset and progression of RSV, particularly in the early phases of inflammation, and persistent elevations of these cytokines usually indicate unsatisfactory prognosis (Tabarani et al, 2013;Vázquez et al, 2019). Previous studies reported that TNF-α, IL-1β, and IL-6 levels were elevated in RSV-induced lung inflammation (Lin et al, 2021). Herein, RSV notably increased the levels of TNF-α, IL-1β, and IL-6 in lung tissue and BALF.…”

Anti-inflammatory activities of Qingfei oral liquid and its influence on respiratory microbiota in mice with ovalbumin-induced asthma

“…The best effect was delivered by QF at a medium dose. QF has been widely used in the treatment of pediatric respiratory diseases in China and has been approved by the Chinese National Drug administration ( Lin et al, 2021 ). Children aged about 6 years old should take one dose (crude drug 91 g) daily, which is equivalent to the medium dose of mice according to the conversion method of body surface area between mice and human.…”

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

“…Combining network pharmacology with molecular docking can serve as a strategy to unveil the underlying mechanisms of multiple compounds and targets of QXZKG (Wang, Li, et al, 2023). Understanding biological processes (BPs) is fundamental to network pharmacology, involving various biological information, such as protein targets and lipids (Lin et al, 2021). Lipidomics encompasses the comprehensive analysis of lipids and their biological activities, providing valuable insights into diverse physiological and pathological process (Chen et al, 2023).…”

“…Understanding biological processes (BPs) is fundamental to network pharmacology, involving various biological information, such as protein targets and lipids (Lin et al, 2021). Lipidomics encompasses the comprehensive analysis of lipids and their biological activities, providing valuable insights into diverse physiological and pathological process (Chen et al, 2023).…”

“…Thus, it is imperative to fully understand the relationship between ALI and pulmonary lipids, as well as the impact of QXZKG on ALI-induced lipid disturbance. The integration of network pharmacology and lipidomics facilitates the identification of active compounds, potential targets, and lipid profiles, thereby enhancing our understanding of the pharmacological mechanisms of QXZKG in the treatment of ALI (Lin et al, 2021).…”