Exploring the mechanism of action of Shengxuening for the treatment of β-thalassemia based on network pharmacology and experimental validation
OBJECTIVE To explore the treatment of Shengxuening β-the mechanism of thalassemia.METHODS Accord-ing to the literature data,the active components and related targets of the main components of shengxuening,silkworm sand,andβ-thalassemia related disease targets were searched by using the corresponding database.Cross-tabulation analysis of drug thera-peutic targets and disease targets was performed to obtain core cross-tabulation targets.The core intersection target information was used for protein interaction network analysis,KEGG and GO enrichment analysis.K562 cells were cultured with different concentrations(100,200,400,800 μg·mL-1)of raw hematoxylin.cell viability was measured by CCK-8 method,and fetal hemo-globin expression level of K562 cells was measured by combined Elisa and Western blot,and real-time fluorescence quantitative analysis(Real-Time PCR)to detect Gγ and Aγ mRNA expression.K562 cells were treated with P38,ERK,JNK specific inhibi-tors in combination with biotin.Elisa was used to detect cellular HbF content,Western blot to detect cellular HbF,P-P38/P38,P-ERK/ERK,P-JNK/JNK expression levels,and q-PCR to detect Gγ,Ay mRNA expression.RESULTS Network pharmacol-ogy determined that Shengxuening can treat β-thalassemia through the MAPK signaling pathway.Molecular experiments deter mined that Shengxuening was effectively administered at a dose of 400 μg·mL-1 for 48 h.Shengxuening promoted Gγ and AγmRNA expression and increased intracellular HbF content through activation of the P38 MAPK signaling pathway,.Compared with the control group,HbF content and Gγ and Ay levels were significantly increased in the experimental group.CONCLUSION Shengxuening promotes fetal hemoglobin synthesis by activating the gamma-cadherin gene through the P38 MAPK signaling pathway.
NETL
NSTL
万方数据
维普
