Analysis of Medication Rules and Mechanism of Core Herb Pairs in Traditional Chinese Medicine for Treating Type 2 Diabetes Mellitus with Spleen Qi Deficiency Syndrome Based on Data Mining and Network Pharmacology
Abstract: Objective: To analyze the medication rules of traditional Chinese medicine (TCM) in treating type 2 diabetes mellitus( T2DM) with spleen qi deficiency syndrome based on data mining,and to explore the mechanism of action of core herb pairs using network pharmacology. Methods: Retrospective analysis was conducted on medical records of patients diagnosed with T2DM with spleen qi deficiency syndrome in the Department of Endocrinology, Guangdong Provincial Hospital of Traditional Chinese and Western Medicine from January 2023 to December 2024. Frequency analysis, nature-flavor-channel entry statistics, association rule analysis, and cluster analysis were performed on Chinese herbal medicine prescriptions to summarize medication rules. Network pharmacology and molecular docking technology were used to predict the potential mechanism of the core herb pair. Results:A total of 190 patient medical records were included, involving 212 Chinese herbal medicines. The core natures and flavors of commonly used Chinese herbal medicines were mainly sweet and warm, with channel entry mainly in the lung and spleen channels. Association rule analysis showed a strong correlation among four herbs: Atractylodis Macrocephalae Rhizoma,Poria,Codonopsis Radix,and Citri Reticulatae Pericarpium. Cluster analysis identified five groups of highfrequency co-occurring herbs. The core herb pair was confirmed as Atractylodis Macrocephalae Rhizoma,Poria,Citri Reticulatae Pericarpium,and Codonopsis Radix. A total of 48 active components of the core herb pair,154 herb pairrelated targets,1 435 disease targets,and 75 common targets between the herb pair and the disease were screened out. Protein-protein interaction (PPI) network analysis revealed the top five key active components:Luteolin,7-Methoxy- 2-methylisoflavone, Naringenin, Nobiletin, and Stigmasterol; the core targets were AKT Serine/Threonine Kinase 1 (AKT1), Tumor Necrosis Factor (TNF), Interleukin-6 (IL-6), Tumor Suppressor Protein p53 (TP53), and Peroxisome Proliferator-Activated Receptor γ (PPARG). Gene Ontology (GO) functional analysis involved biological processes such as response to xenobiotic stimulus, negative regulation of apoptotic process, and RNA polymeraseⅡ transcription;cellular components including extracellular space,plasma membrane,and protein complex;molecular functions such as identical protein binding,enzyme binding,protein homodimerization activity,and zinc ion binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis mainly involved signaling pathways such as cancer,lipid and atherosclerosis,IL-17,and endocrine resistance. The molecular docking binding energies between the top five core targets and the top five key active components of the herb pair were all < -5.0 kcal/mol. Conclusion: Chinese herbal medicines treatment of T2DM with spleen qi deficiency syndrome is mainly based on tonic herbs, combined with urination-promoting and dampness-eliminating, qi-regulating and phlegm-resolving herbs to achieve the effect of strengthening the spleen and dispelling dampness. Among them, Atractylodis Macrocephalae Rhizoma, Poria, Citri Reticulatae Pericarpium, and Codonopsis Radix are the core herb pair for the treatment principle of strengthening the spleen and dispelling dampness. Through components such as Luteolin, 7-Methoxy-2- methylisoflavone, Naringenin, Nobiletin, and Stigmasterol, they act on targets including AKT1, TNF, IL-6, TP53, and PPARG, regulating signaling pathways such as inflammation, metabolic pathways, insulin, and lipid metabolism,thereby exerting a therapeutic effect on T2DM.