The dominant paradigm of “one gene, one target, one disease” has influenced many aspects of drug discovery strategy. However, in recent years, it has been appreciated that many effective drugs act on multiple targets rather than a single one. As an integrated multidisciplinary concept, network pharmacology, which is based on system biology and polypharmacology, affords a novel network mode of “multiple targets, multiple effects, complex diseases” and replaces the “magic bullets” by “magic shotguns.” Chinese herbal medicine (CHM) has been recognized as one of the most important strategies in complementary and alternative medicine. Though CHM has been practiced for a very long time, its effectiveness and beneficial contribution to public health has not been fully recognized. Also, the knowledge on the mechanisms of CHM formulas is scarce. In the present review, the concept and significance of network pharmacology is briefly introduced. The application and potential role of network pharmacology in the CHM fields is also discussed, such as data collection, target prediction, network visualization, multicomponent interaction, and network toxicology. Furthermore, the developing tendency of network pharmacology is also summarized, and its role in CHM research is discussed.

Highlights d SETD2-mediated EZH2-K735me1 licenses EZH2 destruction to impede PCa metastasis d Cancer-associated SETD2 mutation (R1523H) disrupts SETD2-EZH2 interaction d Metformin treatment might combat EZH2-high PCa by stimulating SETD2 expression

-The classic toxicity of carbon tetrachloride (CCl 4 ) is to induce liver lesion and liver fibrosis. Liver fibrosis is a consequence of chronic liver lesion, which can progress into liver cirrhosis even hepatocarcinoma. However, the toxicological mechanisms of CCl 4 -induced liver fibrosis remain not fully understood. We combined transcriptomic and proteomic analysis and biological network technology, predicted toxicological targets and regulatory networks of CCl 4 in liver fibrosis. Wistar rats were treated with CCl 4 for 9 weeks. Histopathological changes, hydroxyproline (Hyp) contents, serum ALT and AST in the CCl 4 -treated group were significantly higher than that of CCl 4 -untreated group. CCl 4 -treated and -untreated liver tissues were examined by microarray and iTRAQ. The results showed that 3535 genes (fold change ≥ 1.5, P < 0.05) and 1412 proteins (fold change ≥ 1.2, P < 0.05) were differentially expressed. Moreover, the integrative analysis of transcriptomics and proteomics data showed 523 overlapped proteins, enriched in 182 GO terms including oxidation reduction, response to oxidative stress, inflammatory response, extracellular matrix organization, etc. Furthermore, KEGG pathway analysis showed that 36 pathways including retinol metabolism, PPAR signaling pathway, glycolysis/gluconeogenesis, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabolism. Network of protein-protein interaction (PPI) and key function with their related targets were performed and the degree of network was calculated with Cytoscape. The expression of key targets such as CYP4A3, ALDH2 and ALDH7A1 decreased after CCl 4 treatment. Therefore, the toxicological mechanisms of CCl 4 -induced liver fibrosis may be related with multi biological process, pathway and targets which may provide potential protection reaction mechanism for CCl 4 detoxication in the liver.