Study on the action mechanism of the Fujin Shengji (FJSJ) Powder on diabetic ulcer based on network pharmacology and molecular docking

Abstract

Abstract Background and Objectives: Fujin Shengji (FJSJ) Powder is mainly used for treating all kinds of canker sores and gangrene. However, there are relatively few studies on the treatment of diabetic ulcer (DU) with FJSJ Powder, and the mechanism is uncertain. This study aimed to explore the potential mechanism of FJSJ Powder in the treatment of DU using network pharmacology and molecular docking. Methods: The main active ingredients and targets for the FJSJ Powder were obtained from the TCMSP database and the published reports. Diabetic ulcer-related targets were searched from the Genecards, Disgenet, Drugbank, OMIM and TTD database. The intersection targets of FJSJ Powder and diabetic ulcer were considered as potential therapeutic targets. The Metascape online database was used for the GO and KEGG enrichment analyses. And then, the protein-protein interaction (PPI) network, herb-ingredient-target-disease (H-I-T-D) network, and herb-ingredient-target-pathway (H-I-T-P) network were constructed. Finally, we used AutoDock Vina and PyMOL software to investigate the molecular docking of the top 15 key active chemical ingredients to the top 15 key target proteins in the PPI network. Result: We collect all the 800 potential targets for 100 active ingredients in FJSJ Powder, 862 diabetic ulcer-related targets, and yielded 196 potential therapeutic targets and 76 key potential therapeutic targets of the FJSJ Powder for DU treatment. A total of 2597 terms of GO enrichment analysis were obtained, including 2284 BP terms, 100 CC terms, and 213 MF terms. A total of 210 enriched KEGG pathways were identied, including AGE-RAGE, PI3K-AKT, HIF-1, MAPK, and TNF signaling pathway. The molecular docking demonstrated that boswellic acid compounds such as AKBA, ABK, α-boswellic acid, β-boswellic acid have low binding energy to several genes. Conclusions: FJSJ Powder regulates DU treatment via a multitarget, component, and signal pathway with a cooperative and bidirectional regulatory mechanism. Its active ingredients may treat DU by regulating the expression of IL6, TNF, AKT1, VEGFA, IL1B, CASP3, PPARG, TP53, and other targets, as well as activating or inhibiting AGE-RAGE, PI3K-AKT, HIF-1, MAPK, and TNF signaling pathways, which exerts immunomodulatory functions, inhibits trauma inflammation and promotes endothelial cell proliferation and migration in order to promote wound healing. This provides new insights for further experiments on the pharmacological effects of FJSJ Powder.