Network Pharmacology-Based Exploration of the Mechanism of Action and Experimental Validation of Yufu Jiedu Ointment(玉肤解毒膏)in the Treatment of Capecitabine-Induced Hand-Foot Syndrome
Network Pharmacology-Based Exploration of the Mechanism of Action and Experimental Validation of Yufu Jiedu Ointment(玉肤解毒膏)in the Treatment of Capecitabine-Induced Hand-Foot Syndrome
Objective:To exploring the mechanism of Yufu Jiedu ointment in the treatment of capecitabine-induced hand foot syndrome(HFS)based on network pharmacology and in vivo experiment validation.Methods:UPLC-Q-TOF-MS was used to identify the chemical constituents of Yufu Jiedu ointment.TCMSP,PubChem and Swiss target prediction databases were used to screen the active ingredients and targets of Yufu Jiedu ointment.String platform was used to analyze the protein interactions.GeneCards database was used to screen the targets related to HFS.GO functional analysis and KEGG signaling pathway enrichment analysis were carried out according to Metascape database.And AutoDocktools software was used to validate the molecular docking of the active ingredients and the core target points.A rat model of HFS was constructed,and Western blotting was used to detect the effects of Yufu Jiedu ointment and urea ointment on the protein expression levels of histone deacetylase 6(HDAC6)and toll-like receptor 4(TLR4)in the plantar skin of HFS rats.Results:A total of 97 active ingredients,304 targets and 45 targets intersecting with HFS were obtained from the screening of Yufu Jiedu ointment.The key targets were mainly enriched in Toll-like receptor signaling pathway,Neutrophil extracellular trap formation,Rap1 pathway and other signaling pathways.The active ingredients,Loureirin A,Fisetin,Pinocembrin,Pterostilbene and Genkwanin,have good binding activity and good stability with the core targets,including HDAC6,histone deacetylase 2(HDAC2),histone deacetylase 1(HDAC1),histone deacetylase 4(HDAC4),signal transducer and activator of transcription 3(STAT3)and cathepsin D(CTSD).In vivo experiments showed that Yufu Jiedu ointment significantly reduced the levels of HDAC6 and TLR4 protein expression in the plantar skin of HFS rats.Conclusion:Yufu Jiedu ointment may reduce neuroinflammatory responses and exert therapeutic effects on HFS by modulating HDAC6 and TLR4 expression.
维普
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