In recent years, diabetic foot has become a significant cause of disability and mortality among individuals with diabetes. With the progression of time and technology, both modern medicine and traditional Chinese medicine have gradually deepened their understanding and research into diabetic foot, further enhancing the treatment methods available for this condition. To a certain extent, this can alleviate patients' pain and improve their quality of life.

To explore the mechanism of Simiao Yong’an Decoction (SYD) in the treatment of diabetic foot (DF).

Databases and software such as TCMSP, GeneCards, OMIM, and TTD were used to identify the pharmacodynamic material basis, therapeutic targets, and metabolic pathways of SYD in the treatment of DF. The serum metabolomics of SYD was integrated with network pharmacology to validate the potential active components and metabolic pathways involved in SYD’s intervention in DF.

The main active components of SYD in treating DF were found to be luteolin, quercetin, and formononetin. The treatment may act through targets such as AKT1, TNF, HSP90AA1, MAPK8, and STAT3, regulating pathways including the MAPK signaling pathway, TNF signaling pathway, phosphatidylinositol signaling pathway, HIF-1 signaling pathway, and Toll-like receptor signaling pathway. The phosphatidylinositol signaling pathway was consistent with the findings from serum metabolomics analysis of SYD.

The phosphatidylinositol signaling pathway may be a key metabolic pathway in the intervention of DF by SYD.