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
Objective To investigate the effect of Erhuang decoction on TGF-β1 expression of lung tiusses and the concentrations of IL-33 in asthmatic rats. Methods Fifty Sprague-Dawley rats were randomly divided into five groups equally:Control group, Asthmatic group, Budesonide aerosol group, High-dose Erhuang decoction group ( 68 g/kg)and Low-dose Erhuang decoction group(17 g/kg). The model of asthma was established by ovalbumin (OVA) sensitizing and challeng-ing. Then Erhuang decoction and budesonide aerosol was used respectively for intervention therapy. Histologic HE staining were used to observe the general pathologic alteration and to analyze the total bronchial wall area (Wat) and the muscle wall area(Wam). The protein expressions of TGF-β1 in the lung tissues were detected by immunohistochemistry. The concentra-tions serum IL-33 and BALF were tested by sandwich ELISA. Results There was significant reduction in the infiltrated inflammatory cells in all drug intervention groups compared with asthma group;The Wat and Wam in asthmatic group was significantly higher in than those in Budesonide aerosol group,High-dose Erhuang decoction group and Low-dose Erhuang decoction group ( Watμm2/μm:54.99±8.82, 52.28±7.61, 58.53±7.63 vs 79.50±5.64, P＜0.05;Wamμm2/μm:22.74±2.73, 20.63±1.72, 21.20±4.50 vs 30.16±1.68, P＜0.05);Compared with control group, BALF and serum IL-33 concentration were significantly higher in asthmatic group. Compared with asthmatic group, all the indicators were significantly decrease in the treatment groups after drug intervention (P＜0.05). Andthere was no significant difference between the treatment groups in all the indicators. TGF-β1 expression in lung tissues in asthmatic group were significantly higher than that in control group (12.60 ± 2.25 vs 1.67 ± 0.17). Compared with asthmatic group, there was significantly reduction of TGF-β1 expression in the Budesonide aerosol group (5.51±2.48), High-dose Erhuang decoction group (5.22±2.52) and Low-dose Erhuang decoction group (6.92 ±2.18) (P＜0.05). There were no significant difference between the treatment groups. TGF-β1 expression and se-rum IL-33 concentration in asthmatic rats were positively correlated with Wat and Wam. Conclusion The effects of Er-huang decotion on ameliorating the progression of airway remodeling about asthmatic rats may be partially by regulating TGF-β1 and IL-33.