Abstract
Wei-Fu-Chun (WFC) tablet is a commercial medicinal product approved by China Food and Drug Administration, which is made of Panax ginseng C.A.Mey., Citrus aurantium L., and Isodon amethystoides (Benth.). WFC has been popularly used for the treatment of precancerous lesions of gastric cancer (PLGC) in clinical practice. In this study, a UHPLC-ESI-Q-TOF/MS method in both positive and negative ion mode was employed to rapidly survey the major constituents of WFC. 178 compounds including diterpenoids, triterpenes, sesquiterpenes, flavonoids, saponins, phenylpropanoids, lignans, coumarins, organic acids, fatty acids, quinones, and sterols, were identified by comparing their retention times, accurate mass within 5 ppm error, and MS fragmentation ions. In addition, 77 absorbed parent molecules and nine metabolites in rat serum were rapidly characterized by UHPLC-ESI-Q-TOF/MS. The network pharmacology method was used to predict the active components, corresponding therapeutic targets, and related pathways of WFC in the treatment of PLGC. Based on the main compounds in WFC and their metabolites in rat plasma and existing databases, 13 active components, 48 therapeutic targets, and 61 pathways were found to treat PLGC. The results of PLGC experiment in rats showed that WFC could improve the weight of PLGC rats and the histopathological changes of gastric mucosa partly by inhibiting Mitogen-activated protein kinase (MAPK) signaling pathway to increase pepsin secretion. This study offers an applicable approach to identify chemical components, absorbed compounds, and metabolic compounds in WFC, and provides a method to explore bioactive ingredients and action mechanisms of WFC.
Highlights
Traditional Chinese medicine (TCM) is based on the principle of holism, that is, all the body systems are interconnected
According to the GO enrichment analysis results, we found that the functions of therapeutic targets were involved in multiple biological processes such as peptide chain serine phosphorylation, RNA polymerase II promoter transcription, cellular hypoxia, apoptosis, vascular endothelial cell migration, macrophage differentiation, vascular endothelial growth factor receptor, chemokine biosynthesis, cell proliferation, and nitric oxide biosynthesis (Figure 3)
The results showed that PI3K/Akt pathway, Mitogen-activated protein kinase (MAPK) pathway, vascular endothelial growth factor (VEGF) pathway, hypoxiainducible factor-1 (HIF-1) pathway, tumor necrosis factor (TNF) pathway, and FOXO pathway may be involved as the anti-precancerous lesions of gastric cancer (PLGC) pathways of WFC
Summary
Traditional Chinese medicine (TCM) is based on the principle of holism, that is, all the body systems are interconnected. The Wei-Fu-Chun (WFC) tablet, a well-known Chinese herbal preparation, is composed of three herbs: P. ginseng (HS: 131 g), C. aurantium (ZQ: 250 g), and I. amethystoides (XCC: 2,500 g). Dosage of these herbs was derived from Chinese Pharmacopoeia, 2020 edition. No studies on the action mechanism of WFC in the treatment of PLGC have been conducted so far. With the prominence of network pharmacology in system biology, this distinct and novel approach to the study of complex analytical systems is becoming more widely known and more frequently used in the field of drug research. We attempted to explore the action mechanisms of WFC in the treatment of PLGC using network pharmacology and experimental studies
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