Network pharmacology and experimental study of compound Phellodendron liquid in treating diabetic foot ulcer
LI Yu-feng，YU Min，SUN Wei-hao
Abstract:
Objective To explore the therapeutic effect of compound Phellodendri liquid in treating diabetic foot ulcer (DFU) based on network pharmacology and experimental study. Methods The active components and related targets of Compound Phellodendri Liquid were screened by Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP). GeneCards and OMIM databases were used to search for diabetic foot ulcer disease targets. The network diagram of “active ingredient-target” was constructed by Cytoscape 3.9.1 software. Intersection targets between drug components and disease was taken by Venny 2.1.0 to and the common target protein interaction network was constructed by STRING 11.0 database platform. GO enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID database. Thirty SPF Sprague-Dawley(SD)male rats were randomly divided into normal ulcer group, diabetic foot ulcer group and Phellodendri Liquid treatment group, with 10 rats in each group. The expression levels of TNF-α, IL-1β, IL-6, VEGF and EGF were detected by ELISA and foot ulcer healing was observed by HE staining. Results 88 active ingredients and 518 active ingredient targets were retrieved by the network pharmacology and 225 drug active ingredients and disease intersection targets were retrieved. 15 key targets were obtained, including TNF-α, IL-6, VEGFA, IL-1β, EGF, CXCL8, etc. GO function enrichment analysis included positive regulation of cytokine activity and growth factor activity. KEGG pathway enrichment analysis included MAPKA signaling pathway, TNF signaling pathway, IL-17 signaling pathway and AGE-RAGR signaling pathway. The results of animal experiments indicated that compared with diabetic foot ulcer group the levels of VEGF and EGF were increased and the contents of inflammatory factors TNF-α, IL-6 and IL-1β were significantly decreased in Phellodendri liquid treatment group. HE?staining revealed that compared with diabetic foot ulcer group the contents of granulation tissue and fibroblast were increased in the treatment group. Conclusion Compound Phellodendron liquid can treat diabetic foot ulcers through multiple pathways, multiple targets and multiple pathways It is verified that compound Phellodendron liquid promots the healing of diabetic foot ulcers by reducing the levels of inflammatory factors TNF-α, IL-6 and IL-1β and increasing the expression of VEGF and EGF to accelerate granulation tissue production.
