Objective To explore the syndrome differentiation and medication, and formulation rules of renowned traditional Chinese medicine (TCM) practitioners in treating type 2 diabetes mellitus (T2DM) using data mining technology, and validate the efficacy of the identified core formula using an animal model. Methods A total of 200 medical cases of T2DM treated by famous TCM practitioners were collected from databases such as China National Knowledge Infrastructure (CNKI), Wangfang, VIP. A database was established using the TCM Inheritance Computing Platform (V3.5). The silhouette coefficient was introduced to evaluate K-means clustering performance, and hierarchical clustering was used for cross-validation to screen for core formulas. For the experimental validation, 40 male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10 each): control, model, core formula, and metformin. Except for the control group, T2DM models with “qi-yin deficiency” syndrome were induced by a 4-week high-fat and high-sugar diet combined with daily oral administration of Qingpi Fuzi decoction (15.75 g/kg), followed by an intraperitoneal injection of streptozotocin (STZ, 30 mg/kg). After successful modeling, the core formula group received the core formula (10.5 g/kg), and the Metformin group received metformin (200 mg/kg) via gavage daily; Control and Model groups received equal volumes of saline, each group was given the drug once a day for four weeks of intervention. Body weight (BW) and fasting blood glucose (FBG) were monitored during the administration period. Serum levels of insulin (INS), glycated hemoglobin (IFCC-HbA1c), interleukin-1β (IL-1β), IL-6, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by ELISA. The proportion of insulin-positive areas was assessed via immunohistochemical staining. Oil red O staining was used to observe lipid deposition in the liver. PAS staining was used to evaluate the pathological changes of renal tissue. Protein expressions of the phosphatidylinositol-3-hydroxykinase (PI3K)/protein kinase B (Akt), nuclear factor-κB (NF-κB), nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways in liver tissues were detected by Western blotting. Results Data mining revealed that qi-yin deficiency was the primary syndrome of T2DM. High-frequency herbs included Huangqi (Astragali Radix), Huanglian (Coptidis Rhizoma), and Fuling (Poria). The medicinal properties were predominantly cold, warm, and neutral, while flavors were mainly sweet, bitter, and pungent, targeting the spleen, lung, and liver meridians. These types of drugs such as tonifying deficiency, clearing heat, promoting diuresis, and activating blood circulation were most prevalent. Association rule analysis identified Astragali Radix-Gengen (Puerariae Lobatae Radix) and Astragali Radix-Coptidis Rhizoma as core herb pairs. Clustering identified a core formula consisting of Astragali Radix, Shanyao (Dioscoreae Rhizoma), Puerariae Lobatae Radix, Shanzhuyu (Corni Fructus), and Poria. In vivo experiments showed that the core formula group had significantly lower FBG, INS, and IFCC-HbA1c levels compared to the Model group (P < 0.05, 0.01, 0.001), with a gradual recovery in BW. Furthermore, IL-1β and IL-6 were significantly decreased (P < 0.01, 0.001), SOD was increased (P < 0.01), and MDA was decreased (P < 0.05). Pathologically, the core formula group showed a significantly higher ratio of insulin-positive area (P < 0.05), reduced hepatic lipid deposition (P < 0.01), and lower renal pathological injury scores (P < 0.05). Western blotting analysis indicated that core formula significantly up-regulated the expression of p-PI3K/PI3K, p-Akt/Akt, Nrf2, and HO-1 (P < 0.05, 0.01), while down-regulating p-NF-κB p65/NF-κB p65 (P < 0.05). Conclusion The core formula exhibits a definite hypoglycemic effect. Its mechanism of action is associated with activating the PI3K/Akt signaling pathway to enhance insulin sensitivity, inhibiting NF-κB-mediated pro-inflammatory responses, and up-regulating the Nrf2/HO-1 pathway to ameliorate oxidative stress. This formula effectively maintains the number and structure of pancreatic islet cells and protects liver and kidney tissues from diabetic pathological damage, providing a scientific basis for the prevention and treatment of T2DM with TCM.

type 2 diabetes mellitus  /  data mining  /  experience of renowned doctors  /  medication principles  /  Astragali Radix-Dioscoreae Rhizoma-Puerariae Lobatae Radix-Corni Fructus-Poria