Network pharmacology-based approach to investigate the mechanisms of Yiyi Fuzi Baijiang Powder in the treatment of malignant tumors

Objective:To systematically investigate the main active components,targets,target-related diseases and action mechanism of Yiyi Fuzi Baijiang powder(YFBP)of Zhang Zhongjing,a Chinese physician of Eastern Han Dynasty of China(3 century A.D.)using the method of network pharmacology.Methods:The active components of YFBP were identified from several databases(TCMSP,TCM Database@Taiwan and TCMID).The potential active compounds were screened based on oral bioavailability and drug-like index in the TCMSP database.DrugBank,TCMSP,and TCMID database searches were performed to predict target-related diseases.Biological functions and KEGG pathway outcomes of all potential targets were analyzed using the DAVID database.Results:A total of 24 active compounds of YFBP,133 related targets,and 305 potential related diseases were obtained.These results showed that YFBP may treat inflammation,pain,and cancer.The functional enrichment analysis indicated that YFBP probably exerts its therapeutic effects by regulating neuroactive ligand-receptor interactions,the TNF signaling pathway,and the PI3K-Akt signaling pathway.Conclusion:This study provides preliminary confirmation that YFBP has the great potentials to treat inflammation,pain,and tumors,which supports Zhang Zhongjing’s original intention to treat intestinal carbuncle with ancient prescription YFBP,but also provides a scientific basis for its treatment in the malignant tumors.

Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression

Objectives: Ziyin Huatan Recipe(ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer(GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.Methods: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3(RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.Results: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration,invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes(migration and invasion) and protein expression levels elicited by ZYHT.In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.Conclusion: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.