BACKGROUND The aim of our study was to elucidate the biological targets and pharmacological mechanisms for calycosin (CC) against colorectal cancer (CRC) through an approach of system pharmacology. MATERIAL AND METHODS Using a web-based platform, all CRC-causing genes were identified using a database of gene-disease associations (DisGeNET), and all well-known genes of CC identified using the databases of prediction of protein targets of small molecules (Swiss Target Prediction), drug classification, and target prediction (SuperPred). The carefully selected genes of CRC and CC were concurrently constructed by using a database of functional protein association networks (STRING), and use of software for visualizing complex networks (Cytoscape), characterized with production of protein-protein interaction (PPI) network of CC against CRC. The important biological targets of CC against CRC were identified through topological analysis, then the biological processes and molecular pathways of CC against CRC were further revealed for testing these important biotargets by enrichment assays. RESULTS We found that the key predictive targets of CC against CRC were estrogen receptor 2 (ESR2), ATP-binding cassette sub-family G member 2 (ABCG2), breast cancer type 1 susceptibility protein (BRCA1), estrogen receptor 1 (ESR1), cytochrome p450 19A1 (CYP19A1), and epidermal growth factor receptor (EGFR). Visual analysis revealed that the biological processes of CC against CRC were positively linked to hormonal metabolism, regulation of genes, transport, cell communication, and signal transduction. Further, the interrelated molecular pathways were chiefly related to endogenous nuclear estrogen receptor alpha network, forkhead box protein A1 (FOXA1) transcription factor network, activating transcription factor 2 (ATF2) transcription factor network, regulation of telomerase, plasma membrane estrogen receptor signaling, estrogen biosynthesis, androgen receptor, FOXA transcription factor networks, estrogen biosynthesis, and phosphorylation of repair proteins. CONCLUSIONS Use of system pharmacology revealed the biotargets, biological processes, and pharmacological pathways of CC against CRC. Intriguingly, the identifiable predictive biomolecules are likely potential targets for effectively treating CRC.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Rong Li1, *, Chao Guo2, *, Xinmou Wu4, Zhaoquan Huang1, 3 and Jian Chen1 1Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guangxi, Guilin 541004, PR China 2Department of Pharmacy, Guigang City People’s Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi 537100, PR China 3Department of Pathology, Affiliated Hospital of Guilin Medical University, Guangxi, Guilin 541004, PR China 4Department of Pharmacy, Guangxi Medical University, Guangxi, Nanning 530021, PR China *These authors share senior authorship Correspondence to: Jian Chen, email: chjian80726@163.com Zhaoquan Huang, email: hospital_huang@126.com Keywords: acetaminophen, liver impairment, biomarker, FGF21 Received: January 25, 2017 Accepted: May 06, 2017 Published: May 18, 2017 ABSTRACT Acetaminophen (APAP) is a common medication that induces hepatocellular damage in a time- or dose-dependent manner. Fibroblast growth factor 21 (FGF21) exerts a series of biological effects, including cellular repair. Compared to clinical diagnosis parameters, we aimed to evaluate whether FGF21 can serve as a sensitive biomarker for APAP-induced liver impairment. In the present study, we discussed comparable data from APAP-treated patients and parallelly established APAP-exposed mice for investigation. The resulting human serological data showed that APAP-treated patients have a visible reduction of FGF21 expression in undetected liver impairment of clinical diagnosis. In the animal study, APAP-exposed livers exhibited normal metabolic functions and liver functions, as revealed by biochemical test and histopathological examination. Endogenous FGF21 concentrations in APAP-treated mice were decreased in sera and liver cells. Moreover, comparable immunoassay data showed that hepatocellular FGF21 expression was reduced in a time-dependent manner. Taken together, these findings elucidate the involvement of abnormal FGF21 expression in early APAP-induced liver impairment. Interestingly, FGF21 may be a promising biomarker of APAP-exposed livers.