Purpose: This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification. Methods: Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments. Results: A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway. Conclusion: This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.

Ulcerative colitis (UC) is a recurring inflammatory bowel disease, in which oxidative stress plays a role in its progression, and regulation of the oxidative/antioxidative balance has been suggested as a potential target for the treatment of UC. The aim of this study was to evaluate the protective effect of andrographolide against UC and its potential antioxidant properties by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Dextran sulfate sodium (DSS) -induced UC mice and the LPS-induced HT29 inflammatory cell model were established to uncover the potential mechanisms of andrographolide. ML385, a Nrf2 inhibitor, was used in both models to assess whether andrographolide exerts a protective effect against UC through the Nrf2/HO-1 pathway. The in vivo experiment showed that andrographolide ameliorated the symptoms and histopathology of DSS-induced mice and restored the expressions of ZO-1, Occludin-1 and Claudin-1. Meanwhile, DSS-induced oxidative stress and inflammation were suppressed by andrographolide treatment, along with the upregulation of key proteins in the Nrf2/HO-1 pathway. In vitro experiments showed that andrographolide attenuated LPS-induced excessive generation of ROS in HT29 cells, reduced inflammatory factors, and upregulated the expression of proteins related to tight junctions and Nrf2/HO-1 pathway. In addition, ML385 abolished the beneficial effect of andrographolide. In conclusion, the protective effect of andrographolide against UC may involve the suppression of oxidative stress and inflammation via the Nrf2/HO-1 pathway.

Purpose: The network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM). Methods: Active ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis. Results: A total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1. Conclusion: This study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.