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 therapeutic effect of gastrin on steroid-associated osteonecrosis (SAON) in rat model. Methods·Twenty-four SD rats were randomly divided into three groups i.e. normal control group (normal group), SAON control group (SAON group) and SAON treatment group (treatment group). SAON group and treatment group were intravenously injected with lipopolysaccharide 1 time per day (600 μg/kg) for 2 d and meanwhile intramuscularly injected with methylprednisolone 1 time per day (50 mg/kg) for 3 d. Normal group was injected with normal saline of the same volumns. After steroid injections, treatment group was injected with gastrin 1 time per day (800 μg/kg) for 14 d, while SAON group was injected with normal saline of the same volumns. After the treatment, bone trabeculas below femoral head growth plate were dissected in the rats for bone histology. Hematoxylin-eosin (H-E) staining, immunohistochemistry, fluorescence staining and Goldner's trichrome staining were applied in this study. Results·SAON model in rats was successfully established. The result of H-E staining showed that compared with SAON group, thrombus area, number and area of fat cells in the bone marrows of treatment group obviously decreased (all P<0.05). Immunohistochemistry showed that osteogenic transcription factor (Sp7) positive cells in treatment group were more than those in SAON group (P<0.01). Compared with SAON group, osteoid length and area (Goldner′s trichrome staining), and bone formation rate and bone mineralization deposition rate (fluorescence staining) all significantly increased in treatment group (all P<0.01). Conclusion·Gastrin can effectively treat SAON in rats by suppressing thrombus and lipid formation and enhancing bone-formation.