Abstract:

This study aimed to discover the molecular mechanism of Fuzheng Tiaoli Decoction based on network pharmacology. The Bioinformatics Analysis Tool of Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) server was used to predict the potential targets of Fuzheng Tiaoli Decoction and construct a compound-target-pathway-disease interaction network diagram. The protein-protein interaction network of key targets was built using the STRING database based on gene ontology (GO), Reactome, and Kyoto encyclopedia of genes and genomes (KEGG) database for biological pathway enrichment analysis. Furthermore, the effect of Fuzheng Tiaoli Decoction on the body weight and eating habit of S180 tumor-bearing mice was studied, and the tumor inhibition rate and thymus and spleen indices were calculated. The results showed that the target network of Fuzheng Tiaoli decoction mainly involves cancer (nonspecific), analgesia, breast cancer, cardiovascular disease, inflammation, prostate cancer, depression, and other diseases and key targets such as OPRK1, NR3C1, NR3C2, ADORA1, ESR1, etc. GO enrichment analysis involved cytosol, cytoplasmic membrane, oxidoreductase activity, transmembrane transport protein activity, cellular amino acid, and other small molecule metabolism processes. Reactome pathway enrichment analysis involved neuronal systems, cross-chemical synapses transmission, neurotransmitter receptors, and post-synaptic signal transmission. KEGG pathway enrichment analysis involved neural activity ligand-receptor interactions, calcium signaling pathways, serotonergic synapses, taste transduction, amino acid metabolism, saliva secretion, etc. Animal experiment results showed that the food intake, mental state, and coat gloss of mice in the low-dose and high-dose groups were better than those in the positive and negative groups. The 28-day body mass growth rate of high-dose groups is higher significant than others, respectively; the tumor suppression rates of the low-dose, high-dose, and positive groups were 8.73%, 19.54%, and 47.89%, respectively.The thymus index of low-dose and high-dose groups is lower than positive group but higher than negative groups significant;the spleen index of high-dose group is lower than positive group significant.This study suggests that Fuzheng Tiaoli Decoction may mediate neural activity ligand-receptor interactions, calcium signaling pathways, serotonergic synapses, taste transduction, amino acid metabolism, salivary secretion, and other signaling pathways by affecting the expression of key target genes and improves anxiety, depression, and other negative mental states. Furthermore, it improves sleep quality, reduces fatigue, improves appetite and nutritional status, enhances immune function, improves the state of splenomegaly and thymus atrophy, enhances the immune function and inhibits tumor progression in tumor-bearing mice. The multi-target characteristics and integral action of Traditional Chinese Medicine compounds provide novel ideas for further research on the molecular mechanism of Fuzheng Tiaoli Decoction.

Key words: Fuzheng Tiaoli Decoction, anti-tumor, immunity, sub-health, network pharmacology