Amethod based on network formulaology and network pharmacology for analyzing the correlation and synergy patterns in the compatibility of Traditional Chinese medicine formulas/prescriptions

Aim: The study aims to explore the synergistic effects between different herbal pairs and the original traditional Chinese medicine prescriptions by developing a model for analyzing compatibility correlation and synergy in prescriptions. Method: We have applied TCMNPAS, a comprehensive analysis platform that integrates network formularology and network pharmacology. This platform is designed to investigate in-depth the compatibility characteristics of TCM formulas and their potential molecular mechanisms. Liuwei Dihuang prescription(LDP), formulated following the principle of "Three Tonics and Three Purgatives," was used as an example. An analysis model built via association network was applied to evaluate the relationship and synergistic impacts between the original prescription and three distinct drug pairs related to specific diseases. Results: Node similarities measured by the nearest-neighbor expansion network and shortest path expansion network between LDP and kidney yin deficiency disease network were 0.873 and 0.685, respectively. The average random walk correlation score between LDP and diseases showed a significant difference, suggesting a strong correlation with diseases. Among these, the herbal pair of Corni FructusMoutan Cortex(SZY-MDP) demonstrated node similarities of 0.742 and 0.433 with kidney yin deficiency on the nearest-neighbor expansion network and shortest path expansion network, respectively. Also, a significant difference was noted in the average random walk correlation score of this pair with diseases, signifying that this herb pair is most closely related to the original prescription and diseases. Simultaneously, within LDP, the SZY-MDP herbal pair showed the closest association with the original prescription concerning shared targets, active compounds, and disease targets. Notably, the most prominent KEGG signaling pathway for LDP intervention in hyperthyroidism was the regulation of adipocyte lipolysis, indicating its regulatory effect on body energy metabolism and lipid metabolism. Conclusion: Based on the analysis model focused on compatibility correlation and synergy, the "tonifying and purgative" drugs in LDP exhibit specific "correlation-synergy" effects on kidney yin deficiency.