Buxuhuayu decoction accelerates angiogenesis by activating the PI3K-Akt-eNOS signalling pathway in a streptozotocin-induced diabetic ulcer rat model

Ethnopharmacological relevance: Buxuhuayu decoction (BXHYD) has been frequently used to treat patients with diabetic ulcers (DUs), without notable adverse reactions. However, the related molecular mechanism remains unelucidated. Aim of the study: This study assessed the potential mechanism of BXHYD against DUs by using network pharmacology and animal experiments. Materials and methods: First, high-performance liquid chromatography (HPLC) was used for quality control of BXHYD. Further, the hub compounds and targets were screened from the Active Compound-Targets (ACT) network and the protein and protein interaction (PPI) network. Enrichment analysis was performed using DAVID, and molecular docking technology was used to identify active compounds that may play a key role in pub targets. Finally, a DUs animal model was established and used to elucidate the effect of BXHYD on the PI3K/Akt/ eNOS signalling pathway. Results: (1) Calycosin-7-glucoside, amygdalin, and tanshinone iiA were detected in the freeze-dried powder of BXHYD. (2) Twelve hub compounds and eight hub targets were screened using the ACT and PPI networks. Through molecular docking, it was found that the four hub targets (TP53, IL6, VEGFA, and AKT1) binds luteolin and quercetin more tightly. (3) BXHYD is most likely to promote angiogenesis and wound healing by activating the PI3K/Akt/eNOS signalling pathway. Conclusions: This research revealed that BXHYD might activate the PI3K/Akt/eNOS signalling pathway to promote DUs healing. These findings support the clinical use of BXHYD and provide the foundation for its subsequent studies.