Determining the mechanism of action of the Qishan formula against lung adenocarcinoma by integration of network pharmacology, molecular docking, and proteomics.

BACKGROUND: Lung adenocarcinoma (LUAD) is the main pathological type of lung cancer. Qishan formula (QSF) is reportedly efficacious against LUAD. However, its mechanisms of action currently remain elusive. Therefore, network pharmacology, molecular docking techniques and proteomics were used to verify the potential pharmacological effects of QSF in the treatment of LUAD. METHODS: The active ingredients and potential targets of QSF were obtained from the TCMSP, chemical source network and construct a drug-component-target networks using Cytoscape v3.7.2. Data for disease targets were obtained from 5 databases: TCGA, OMIM, DrugBank, DisGeNET, and GeneCards. Drug disease cross targets were used to construct protein-protein interaction networks for selecting the core targets using the STRING database and enrichment pathway networks using the DAVID database. Finally, TMT quantitative proteomics was used to identify the possible core targets and action pathways. Molecular docking to verify the affinity between components and targets. RESULTS: Network pharmacology identified core components of QSF against LUAD included baicalein, methylophiopogonone B, quercetin, kaempferol, isorhamnetin, and luteolin, which can act on 10 key targets (SRC, TP53, PIK3R1, MAPK3, STAT3, MAKP1, HSP90AA1, PIK3CA, HRAS, and AKT1). QSF might play a therapeutic role in LUAD by regulating biological processes such as signal transduction, protein phosphorylation, cell proliferation, and apoptosis, as well as the PI3K/AKT, MAPK, FoxO, and other signaling pathways. Proteomics identified 207 differentially expressed proteins, and by integrating with network pharmacology and molecular docking results we found that 6 core components of QSF may target TP53 against LUAD through the PI3K/AKT signaling pathway. CONCLUSION: QSF is a multitarget recipe potentially exerting pleiotropic effects in LUAD.

Photochemistry and pharmacology of 9, 19-cyclolanostane glycosides isolated from genus Cimicifuga.

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9, 19-cyclolanostane triterpenoid glycosides, which often exhibit extensive pharmacological activities. 9, 19-Cyclolanostane triterpenoid glycosides are distributed widely in genus Cimicifuga rather than in other members of the Ranunculaceae family. So far, more than 140 cycloartane triterpene glycosides have been isolated from Cimicifuga spp.. The aim of this review was to summarize all 9, 19-cyclolanostane triterpenoid glycosides based on the available relevant scientific literatures from 2000 to 2014. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.