Network pharmacology and in vivo experiment-based strategy to investigate mechanisms of JingFangFuZiLiZhong formula for ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease, often cause carcinogenesis, disability, and intestinal perforation. The JingFangFuZiLiZhong formula (JFFZLZ) shows a good effect against UC in the clinic. Hence, we aim to investigate the mechanisms between JFFZLZ and UC via network pharmacology data mining and in vivo experiments. METHODS: We obtained active constituents and related targets from public databases. The overlapped genes between JFFZLZ and UC targets were further analysed by enrichment analysis. The active constituents and hub targets were used to construct molecule docking analysis. We finally screened out nine hub targets and their expressions were verified in the Gene Expression Omnibus database and UC rats' colon tissues after JFFZLZ treatment. RESULTS: The results implied that JFFZLZ mainly regulated signal transduction, metabolites production, and inflammation pathways. The expression of STAT3, CXCL8, IL6, CXCL12, TNF, TP53, and PTPN11 were both upregulated in colon tissues of UC patients and UC rats. While RELA, EGFR, and TP53 were downregulated in UC patients, but upregulated in UC rats. Furthermore, JFFZLZ could repair UC rats' colon mucosal damage and promote the healing of ulcers via regulating the hub targets. CONCLUSION: These results elucidated that the anti-UC effect of JFFZLZ was closely related to the inhibition of inflammatory response, inhibition of oxidative stress, and repairing colon mucosal damage through different signal pathways. The findings could contribute to a better understanding of the regulation mechanisms in JFFZLZ against UC.Key messagesJFFZLZ could reduce the inflammatory infiltration and repair UC rats' colon mucosal damage.Through the network pharmacology-based strategy and public database mining, we obtained the hub targets and key pathways between JFFZLF and UC.The mechanism of JFFZLZ against UC was inhibition of inflammatory response and oxidative stress by regulating the expression of the hub targets.

Network Pharmacology and Molecular Docking Study of Zhishi-Baizhu Herb Pair in the Treatment of Gastric Cancer.

OBJECTIVE: This study aimed to investigate the possible mechanism of the Zhishi and Baizhu herb pair in the treatment of gastric cancer by means of network pharmacology and molecular docking and to provide a theoretical basis for experiments and clinical application of traditional Chinese medicine for treating gastric cancer. METHODS: The main active chemical components of Zhishi and Baizhu were screened through Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and selected by using the thresholds of oral bioavailability ≥30% and drug-likeness ≥18%. The targets of Zhishi and Baizhu were obtained from TCMSP, Therapeutic Targets Database (TTD), and the DrugBank database. The corresponding genes of the targets were retrieved from the UniProt database, and the gastric cancer targets were obtained from the GeneCards database and TTD. Subsequently, the networks were built between the main drug components, drug targets, and gastric cancer targets. Then, the enrichment analyses of GO and KEGG were applied to predict the potential roles of gastric cancer pathogenesis via the R package clusterProfiler. Finally, molecular docking was used to determine the affinity between the targets and components. RESULTS: Twenty-seven main active components were predicted from the Zhishi-Baizhu herb pair, and a total of 120 intersection genes were screened from 303 potential medicine genes and 1,839 disease genes. The enrichment included the PI3K-Akt and IL-17 signaling pathways, and the network analysis showed that the Zhishi-Baizhu herb pair acted on seven key targets, namely, AKT1, MMP9, IL-6, CCND1, BCL2, MTOR, and MDM2 (where they played a role in treating gastric cancer). Molecular docking showed that luteolin and naringenin could stably bind to the targets. CONCLUSION: The possible mechanisms of the components of the Zhishi-Baizhu herb pair in treating gastric cancer might be related to luteolin and naringenin, which intervened with the targets AKT1, MMP9, IL-6, CCND1, BCL2, MTOR, and MDM2, and are linked with the PI3K-Akt and IL-17 signaling pathways. This knowledge will lay a solid foundation for further experimental and clinical studies.