Network Pharmacological Analysis Of Salvia Miltiorrhiza Against Leukemia And Cell Test Research Of Miltirone

Objective:To explore the mechanism of Salvia miltiorrhiza against leukemia through network pharmacology and molecular docking.The cytotoxic effect of miltirone on acute monocytic leukemia THP-1 cells was studied through cell experiments.Methods:1.The interaction network of "Salvia miltiorrhiza-active components-targets-acute leukemia" was constructed by network pharmacology.2.The protein-protein interaction(PPI)network of Salvia miltiorrhiza against leukemia was created and essential targets were screened.3.GO functional analysis and KEGG pathway enrichment analysis were performed on the common genes between Salvia miltiorrhiza and leukemia.4.Molecular docking of key active ingredients of Salvia miltiorrhiza with core targets.5.The cytotoxicity of miltirone on THP-1 cells was detected.Results:1.50 compounds and 37 corresponding targets were included in the "Salvia miltiorrhizaactive components-targets-leukemia" network,among which the key targets were TP53、AKT1、STAT3、MYC、JUN、MAPK.2.Biological processes mainly focused on regulation of DNA-binding transcription factors,oxidative stress,aging,response to drugs,etc.The main signaling pathways included chemical carcinogenesis-receptor activation,IL-17,PI3K/AKT,p53,and viral carcinogenesis,etc.3.Molecular docking results showed that tanshinone IIA and AKT1,JUN,Danshexinkum and TP53,STAT3,AKT1,JUN,MAPK1,isotanshinone IIA and STAT3,AKT1,JUN,cryptotanshinone and STAT3,JUN can form strong affinity.4.Cell experiment results showed that cell viability was significantly decreased after treatment of THP-1 cells with 10 μmol/L miltirone for 24 h.RT-PCR results showed that miltirone inhibited the transcription of NCOA2 and PARP1,increased the proportion of Bax/Bcl-2 and the expression level of Caspase-3 mRNA.Caspase family inhibitor Z-VADFMK can attenuate the effect of miltirone-induced apoptosis.Conclusion:1.50 active ingredients of Salvia miltiorrhiza exerted biological effects by acting on 37 targets which may participate in multiple biological processes,such as response to drug,gene transcription,aging,and involve in oncogenic-receptor activation,PI3K/AKT,P53 and other signaling pathways.2.Through molecular docking,it was preliminarily verified that the active small molecules in Salvia miltiorrhiza had good binding to the core target protein,which can provide a direction for the follow-up study of the anti-leukemia mechanism of Salvia miltiorrhiza.3.Miltirone kills THP-1 cells by inhibiting proliferation and promoting apoptosis.