ABSTRACT
Network pharmacological approaches were used to predict the components, targets and pathways of Erhuang decoction (EhD) in the treatment of acute lung injury (ALI). The SwissTargetPrediction platform, DisGeNET, Therapeutic Target Database (TTD), GeneCards and Online Mendelian Inheritance in Man (OMIM) databases were used to predict potential targets of EhD and were integrated with the predicted targets for the treatment of ALI. A protein-protein interaction network model was constructed by using String database and Cytoscape software; the DAVID platform was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of drug components-targets-pathways was constructed by Cytoscape software and the SwissDock platform was used to dock the molecules of EhD found in blood with the key disease targets. An ALI model was established in mice and inflammatory factor detection and Western blot protein expression experiments with lung tissue sections were carried out to verify the effect of EhD in the treatment of ALI. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Shandong University (Grant Number: 2016020). We identified 148 potential targets including signal transducer and activator of transcription 3 (STAT3), vascular endothelial cell growth factor A (VEGFA), RAC-alpha serine/threonine-protein kinase (AKT1), and nuclear factor-kappa B/p65 (RELA). The potential targets are largely associated with the biological processes of inflammation, oxidative stress, and apoptosis. Additional pathways relate to cancer, VEGF signaling, mitogen-activated protein kinase (MAPK) signaling, and Toll-like receptors (TLRs) signaling, along with other signaling pathways. Pharmacodynamic experiments showed that EhD could significantly reduce the content of inflammatory factors and the degree of lung injury of ALI mice. Western blot revealed that EhD could significantly decrease the expression of NF-κB/p65 and upregulate the expression of NF-kappa-B inhibitor alpha (IκBα). From the perspective of network pharmacology, the mechanisms of EhD in the treatment of ALI is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. This research provides a reference for further study of the mechanism of this traditional Chinese medicine.
ABSTRACT
An increase in the number of smokers, severe air pollution and outbreak of respiratory infectious diseases have caused a sharp increase in patients with respiratory diseases, which seriously threatens the safety of human lives and properties. Garlic, as a medicine-food homology plant, is used as a medicine by its bulbs. It has various pharmacological effects such as anti-inflammation, anti-oxidation, blood lipid lowering, blood pressure lowering, and anti-bacterial effects. Furthermore, the main active substances in garlic are organosulfur compounds. In recent years, many studies have reported the significant protective effects of garlic organosulfur compounds on common respiratory diseases. Based on the literatures from Pubmed and Web of Science in the past 5 years, we reviewed the effects and mechanisms of garlic organosulfur compounds against chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, pulmonary fibrosis and lung cancer in this article. The underlying mechanisms consisted of anti-inflammation, anti-oxidation, anti-apoptosis, reducing mucus secretion, inhibiting extracellular matrix synthesis, inhibiting cancer cell metastasis, and reducing cancer stem cells activity. The article was aimed to provide theoretical and experimental evidences for the further development and cli-nical applications of garlic organosulfur compound products.
