Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes that severely impairs quality of life. The Yi-Qi-Bu-Shen Recipe (YQBS) alleviates diabetic complications, but its mechanism against DPN remains unclear. This study aimed to explore the underlying mechanism of YQBS against DPN using network pharmacology and to verify its effects on peripheral nerve injury and modulation of the AGE-RAGE/NF-κB signaling pathway in vivo . Active components of YQBS were computationally screened via the TCMSP database, potential targets were predicted using GeneCards and OMIM, and key pathways were analyzed by KEGG enrichment. Molecular docking was performed to assess binding affinities. In animal experiments, streptozotocin-induced DPN rats were randomized into control, model, low-dose YQBS, and high-dose YQBS groups. After 12 weeks, nerve conduction velocity, sciatic nerve pathology, nerve repair–related proteins, and RAGE/NF-κB p65 phosphorylation were evaluated. Network pharmacology predicted quercetin, β-sitosterol, and formononetin as major active components, PTGS2 and NOS2 as core targets, and AGE-RAGE/PI3K–Akt as key pathways. Molecular docking predicted favorable binding affinities. Animal experiments confirmed that YQBS significantly improved nerve conduction, alleviated nerve damage, upregulated repair proteins, and inhibited RAGE expression and NF-κB p65 phosphorylation. In conclusion, YQBS ameliorates DPN in rats, with suppression of AGE-RAGE/NF-κB pathway activation.
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