To study the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer based on network pharmacology.

The aim of the study wasto explore the target and potential mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer infection by network pharmacology. The target information of baicalein and flavonin was mined from CTD database and Swiss database. Genecards database, DRUGBANK database, and OMIM database were used to search for lung cancer related genes. The target protein network map (PPI) was drawn by using the STRING database analysis and Cytoscape3.7.1 software. With the help of Perl language, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were carried out by using the biological program package of R language. In total, 347 biological targets of Astragaloside and Scutellariae Radix were identified through the collection and analysis of multiple databases. In total, 1526 lung cancer targets were obtained from a multi-disease database. The "component-target" network of Astragaloside and Scutellariae Radix was constructed, and the protein interaction network (PPI) of the overlapping targets was analyzed to identify the key targets of drug-influenced diseases. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer. Scutellariae Radix and Astragaloside have the characteristics of multi-component, multi-target and multi-pathway in the treatment of lung cancer, which provides a new idea and scientific basis for further research on the molecular mechanism of the antilung cancer effect of Scutellariae Radix and Astragaloside.

Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification.

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. This study was designed to uncover the healing effect of friedelin, a bioactive compound against UC through bioinformatics of network pharmacology and experimental verification of UC model mice. MATERIALS AND METHODS: Targets of friedelin and potential mechanism of friedelin on UC were predicted through target searching, PPI network establishing, and enrichment analyzing. We explored effects of friedelin on dextran sulfate sodium (DSS)-induced colitis. Severity of UC was investigated by body weight, disease activity index (DAI), and length of the colon. Inflammation severity was examined by determination of proinflammatory and anti-inflammatory cytokines. The numbers of autophagosome around the epithelial cells were observed by autophagy inhibition via a transmission electron microscope. The expressions of autophagy-related ATG5 protein and AMPK-mTOR signaling pathway were determined by immunofluorescence staining. RESULTS: In this study, 17 potential targets of friedelin and 1111 UC-related targets were identified. 10 therapeutic targets of friedelin against UC were acquired from overlapped targets of UC and friedelin. PPI network construction filtered 14 core targets through target amplification and confidence enhancement. The results of molecular docking showed that the docking scores of the top 5 active targets were higher than the threshold values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out, showing friedelin alleviates UC through anti-inflammatory pathways and molecular function of autophagy. Subsequently, animal-based experiments revealed the intraperitoneal injection of friedelin ameliorated DSS-induced body weight loss, DAI decrease, colon length shortening and colonic pathological damage with lower myeloperoxidase and proinflammatory cytokines (IL-1ß and IL-6) and higher IL-10 levels, and more autophagosomes in transmission electron microscope results. The AMPK-mTOR signaling pathway plays important role in the friedelin's effect in autophagy as KEGG pathway result and experiment verification. Furthermore, the 3 ma validated the role of autophagy as an improvement in the friedelin's pharmacologic effect to UC model mice. CONCLUSIONS: Friedelin ameliorated DSS-induced colitis in mice through of inflammatory inhibition and regulation of autophagy.

Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification.

AIM: The incidence of ulcerative colitis (UC) is increasing steadily in developed countries, it is plaguing nearly 1 million people in the United States and European countries, while developing countries have had a rapidly increased incidence over the past decades. Curcuma is widely used in treating malaria, UC, Crohn's disease, and colon cancer, which lead to diarrhea and bloody stool. However, the systemic mechanism of curcuma in treating UC is still unclear. Our work was supposed to expound how does curcuma alleviate UC in a comprehensive and systematic way by network pharmacology, molecular docking, and experiment verification. METHODS: Traditional Chinese Medicine System Pharmacology Database (TCMSP), Shanghai Chemistry & Chemical Industry Data Platform (SGST), and papers published in Chinese Network Knowledge Infrastructure (CNKI) and PubMed were used to collect the chemical constituents of curcuma based on ADME (absorption, distribution, metabolism, and excretion). And effective targets were predicted by Swiss Target Prediction to establish the curcuma-related database. The disease targets of UC were screened by GeneCards and DrugBank databases, and Wayne (Venn) analysis was carried out with curcuma targets to determine the intersection targets. AutoDock software and TCMNPAS system were used to dock the core chemical components of curcuma with key UC targets. Protein interaction (PPI) network was constructed based on the STRING database and Cytoscape software. Gene function GO analysis and KEGG pathway enrichment analysis were carried out by using Metascape database. Finally, HE staining was performed to identify the inflammatory infiltration and expression difference in TNF-α and STAT3 before and after the treatment of curcuma which was verified by immunoblotting. RESULTS: Twelve active components containing 148 target genes were selected from curcuma. Potential therapeutic targets of curcuma in the treatment of UC were acquired from 54 overlapped targets from UC and curcuma. Molecular docking was used to filter the exact 24 core proteins interacting with compounds whose docking energy is lower than -5.5 and stronger than that of 5-aminosalicylic acid (5-ASA). GO and KEGG analyses showed that these targets were highly correlated with EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, MAPK signaling pathway, and inflammatory bowel disease (IBD). Experiments verified curcuma relieved pathological manifestation and decreased the expression of TNF-α and STAT3. CONCLUSION: Curcuma relieved the colon inflammation of ulcerative colitis via inactivating TNF pathway, inflammatory bowel disease pathway, and epithelial cell signaling in Helicobacter pylori infection pathway, probably by binding to STAT3 and TNF-α.