Food-Herb Dual-Function in Astragali Radix-Poria-Rheum: Network Pharmacology and Database Mining for Diabetic Kidney Disease Mechanisms Exploration.

The growing demand for functional foods derived from medicinal-edible homologous resources offers a promising strategy to address the chronic metabolic dysregulation underlying diabetic kidney disease (DKD), particularly in patients requiring long-term pharmacological interventions. DKD, a metabolic disorder-driven complication of diabetes, is characterized by chronic hyperglycemia, insulin resistance (IR), and systemic metabolic dysregulation, necessitating novel dietary approaches to complement conventional therapies. To systematically explore the therapeutic potential of medicinal-edible homologous herbs in DKD management, this study retrieved clinical literature from the China National Knowledge Infrastructure (CNKI) database, focusing on traditional Chinese medicines (CHMs) with dual dietary and therapeutic functions. By integrating data mining techniques (frequency analysis, attribute-flavor analysis, herb-pair co-occurrence networks, and cluster analysis) with expert clinical consensus, we prioritized the identification of core medicinal-edible homologous combinations that align with DKD's metabolic pathology. This multi-dimensional approach revealed Huangqi (Astragali Radix), Fuling (Poria), and Dahuang (Rhei Radix et Rhizoma) (Ast-Por-Rhe) as the most predictive herb combination, highlighting their synergistic role as functional food-derived agents in mitigating DKD progression. Network pharmacology revealed that Ast-Por-Rhe's bioactive components (e.g., isorhamnetin, 7-O-methyleriodictyol) act as dual-purpose nutrients and metabolic regulators, synergistically targeting 38 DKD-associated genes. Functional enrichment analysis demonstrated Ast-Por-Rhe's capacity to restore metabolic homeostasis by alleviating IR through dephosphorylation modulation, while rectifying PI3K-Akt signaling. In a streptozotocin (STZ)-induced DKD rat model, Ast-Por-Rhe supplementation, as a functional food intervention, significantly mitigated renal metabolic dysfunction, evidenced by enhanced IRS1/PI3K/Akt activity, reduced lipid peroxidation, and improved renal fibrosis. These findings position Ast-Por-Rhe as a paradigm of medicinal-edible homologous functional foods that counteract DKD progression through multi-component synergy, specifically targeting IR-driven metabolic perturbations. This study provides a translational roadmap for developing evidence-based dietary strategies using bioactive food components, advancing the application of medicinal-edible resources in metabolic disorder management.