Mechanism of Yi-Qi-Bu-Shen Recipe for the Treatment of Diabetic Nephropathy Complicated with Cognitive Dysfunction Based on Network Pharmacology and Experimental Validation

Context: Diabetic nephropathy (DN) and cognitive dysfunction (CD) are common complications of diabetes. Yi-Qi-Bu-Shen Recipe (YQBS) can effectively reduce blood glucose, improve insulin resistance, and delay the progression of diabetic complications. The underlying mechanisms of its effects need to be further studied. Objective: This study elucidates the mechanism of YQBS in DN with CD through network pharmacology and experimental validation. Materials and Methods: Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Male Sprague-Dawley (SD) rats were divided into 6 groups: model, YQBS (2, 4, 8 g/kg), positive control (metformin, 200 mg/kg), and control; the DN model was established by high sugar and high fat diet combined with intraperitoneal streptozotocin injection. After the DN model was established, the rats were gavaged for 10 weeks. Serum, kidneys, and hippocampus tissues were collected to measure the expression levels of TLR4, NF-.B, TNF-a, and IL-6. Results: The network pharmacology analysis showed that quercetin and kaempferol were the main active components of YQBS. TNF and IL-6 were the key targets, and TLR4/NF-kappa B pathway was crucial to YQBS in treating DN complicated with CD. Experimental validation showed that the intervention of YQBS can reduce TNF-alpha and IL-6 in serum, and also significantly decreases the protein expression of TLR4 and NF-kappa B. Conclusion: YQBS exerts anti-inflammatory effects on DN with CD through TLR4/NF-kappa B pathway. This study provides a biological basis for the scientific usage of YQBS in inflammation diseases and supplies experimental evidence for future traditional Chinese medicine development.