Exploration of the Molecular Mechanism of Icariin Intervention in Ankylosing Spondylitis Based on Network Pharmacology and Experimental Verification
Objective To explore the potential target of icariin(ICA)in the intervention of ankylosing spondylitis(AS)by using network pharmacology and experimental verification.Methods Network pharmacology and molecular docking were used to predict possible targets and pathways for ICA treatment of AS.A total of 15 active AS patients and 15 gender-and age-matched healthy volunteers were recruited to extract peripheral blood mononuclear cells(PBMCs)for in vitro experiments to detect the expression of janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway related molecules after different concentrations of ICA intervention.Results Transcription factor p65(RELA),nitric oxide synthase(NOS)2,mitogen-activated Protein Kinase(MAPK)14,MAPK 1,insulin-like growth factor(IGF)1,heat shock 70 kDa protein(HSPA)1A,heat shock 90 kDa protein alpha(HSP90A)A1,JAK2 and protein kinase C beta(PRKCB)may be potential targets for ICA regulation of AS.The results showed that the phosphorylation levels of JAK2 and STAT3 in PBMCs of active AS patients were significantly higher than those of control group(P<0.05),the phosphorylation levels of JAK2 and STAT3 in PBMCs of AS patients were significantly decreased after ICA in vitro intervention(P<0.05).The expression of specific transcription factors retinoic acidrelated orphan receptor(ROR)γt and its coding gene RORc in active AS patients was significantly higher than that in the control group(P<0.05),and ICA could down-regulate the expression of RORc protein and RORc mRNA(P<0.05).Conclusion ICA may play a role in the treatment of AS through key targets such as RELA,NOS2,MAPK14,MAPK1,IGF1,HSPA1A,HSP90AA1,JAK2 and JAK2/STAT3 signaling pathway.
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