Study on the Frequent Drugs Used by Master Lu Fang in Treating the Blood Stasis Syndrome of Coronary Heart Disease:a Network Pharmacology

ZHENG Yumeng; ZOU Guoliang; DOU Jinhang; WEI Chunming; QIAN Taoming

doi:10.12102/j.issn.1672-1349.2026.01.013

Abstract：Objective: Based on the three principles of 'differentiating cold and heat when activating blood circulation', 'distinguishing deficiency and excess when activating blood circulation', and 'not forgetting to treat qi when activating blood circulation' proposed by National TCM Master Lu Fang, this study utilized network pharmacology to establish a network relationship between commonly used medicines for treating coronary heart disease with blood stasis syndrome and disease targets through drug databases and target databases. It analyzed the interactions between drug components and targets, verified the efficacy of the drugs on coronary heart disease with blood stasis syndrome, and explored the correlation between drug application and coronary heart disease with blood stasis syndrome, as well as the relationship between drug use and the treatment principles of National TCM Master Lu Fang. Methods: The targets of active components of each drug were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to blood stasis syndrome were obtained from the Chinese Medical Syndrome Ontology and Multidimensional Quantitative Association Calculation Platform (SoFDA). Disease targets related to coronary heart disease were retrieved from the GeneCards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM) databases. Cytoscape 3.10.1 software was used to construct a 'drug-component-target-disease' network. The STRING 12.0 database was used to build a protein-protein interaction (PPI) network of intersecting targets. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: A total of 10 high-frequency herbs—Paeonia suffruticosa bark, Salvia miltiorrhiza, Frankincense, Myrrha, Chuanxiong, Aconite, Angelica sinensis, Rheum palmatum, Astragalus membranaceus, and Evodia rutaecarpa—were screened, with 1,073 targets; 10,301 disease targets; 348 blood stasis syndrome targets; and 51 overlapping targets. PPI network analysis identified core proteins including ABCC8, KCNQ1, and KCNA5, among others. GO enrichment analysis yielded 213 entries. KEGG pathway enrichment analysis showed that the drugs mainly involved pathways such as the advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling pathway in diabetic complications, endocrine resistance, proteoglycans in cancer, congestive cardiomyopathy, and hypertrophic cardiomyopathy. Conclusion: The 10 high-frequency herbs used according to the three principles of 'differentiating cold and heat when activating blood circulation', 'distinguishing deficiency and excess when activating blood circulation', and 'not forgetting to treat qi when activating blood circulation' by National TCM Master Lu Fang are Paeonia suffruticosa bark, Salvia miltiorrhiza, Frankincense, Myrrha, Chuanxiong, Aconite, Angelica sinensis, Rheum palmatum, Astragalus membranaceus, and Evodia rutaecarpa. The treatment of coronary heart disease with blood stasis syndrome mainly involves core proteins such as ABCC8, KCNQ1, and KCNA5, and pathways such as the AGE-RAGE signaling pathway in diabetic complications, endocrine resistance, proteoglycans in cancer, congestive cardiomyopathy, and hypertrophic cardiomyopathy.