Abstract
Objective: To predict and analyze the target of anti-Hepatocellular Carcinoma (HCC) in the active constituents of Safflower by using network pharmacology.
Methods: The active compounds of safflower were collected by TCMSP, TCM-PTD database and literature mining methods. The targets of active compounds were predicted by Swiss Target Prediction server, and the target of anti-HCC drugs was collected by DisGeNET database. The target was subjected to an alignment analysis to screen out Carvacrol, a target of safflower against HCC. The mouse HCC model was established and treated with Carvacrol. The anti-HCC target DAPK1 and PPP2R2A were verified by Western blot and co-immunoprecipitation.
Results: A total of 21 safflower active ingredients were predicted. Carvacrol was identified as a possible active ingredient according to the five principles of drug-like medicine. According to Carvacrol's possible targets and possible targets of HCC, three co-targets were identified, including cancer- related are DAPK1 and PPP2R2A. After 20 weeks of Carvacrol treated, Carvacrol group significantly increased on DAPK1 levels and decreased PPP2R2A levels in the model mice by Western blot. Immunoprecipitation confirmed the endogenous interaction between DAPK1 and PPP2R2A.
Conclusion: Safflower can regulate the development of HCC through its active component Carvacrol, which can affect the expression of DAPK1 and PPP2R2A proteins, and the endogenous interactions of DAPK1 and PPP2R2A proteins.
Keywords: Safflower, carvacrol, network pharmacology, hepatocellular carcinoma, DAPK1, immunoprecipitation.
Graphical Abstract
Animated Abstract
[http://dx.doi.org/10.1631/jzus.B1700156] [PMID: 29971988]
[http://dx.doi.org/10.1007/s00268-018-4698-3] [PMID: 29947980]
[http://dx.doi.org/10.1016/j.jep.2018.11.014] [PMID: 30415058]
[http://dx.doi.org/10.1016/j.prp.2017.01.006] [PMID: 28416328]
[http://dx.doi.org/10.1016/j.biopha.2018.09.086] [PMID: 30551534]
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[http://dx.doi.org/10.1093/nar/gky1021] [PMID: 30380087]
[http://dx.doi.org/10.1093/nar/gkr299]
[http://dx.doi.org/10.1007/978-1-4939-3167-5_2] [PMID: 26519399]
[http://dx.doi.org/10.1093/nar/gkw943] [PMID: 27924018]
[http://dx.doi.org/10.1042/BCJ20160991] [PMID: 28159896]
[http://dx.doi.org/10.1021/acs.jcim.6b00174] [PMID: 27391578]
[http://dx.doi.org/10.1016/j.jep.2019.01.027] [PMID: 30703496]
[http://dx.doi.org/10.5582/bst.2018.01261] [PMID: 30799321]
[http://dx.doi.org/10.3892/ol.2019.9946] [PMID: 30867790]
[http://dx.doi.org/10.1158/1535-7163.MCT-17-1049] [PMID: 29703843]
[PMID: 29480000]
[http://dx.doi.org/10.1002/mc.22893] [PMID: 30136419]
[http://dx.doi.org/10.1002/iub.1879] [PMID: 30419147]
[http://dx.doi.org/10.3892/mmr.2018.8714] [PMID: 29532877]
[http://dx.doi.org/10.18632/oncotarget.7158] [PMID: 26848620]
[http://dx.doi.org/10.4103/0973-1482.154925] [PMID: 27461646]
[http://dx.doi.org/10.1177/0960327117735572] [PMID: 29019276]
[http://dx.doi.org/10.1177/0960327115627688] [PMID: 26801986]